https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Adam+MeadeProteopedia - User contributions [en]2026-09-14T20:08:48ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=Irr&diff=953654Irr2009-05-04T22:59:10Z<p>Adam Meade: New page: '''''Iron Response Regulator (Irr)''''' ---- =Background Information= Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen speci...</p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. To prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref> Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
=Phylogenetic Tree=<br />
<br />
http://consurf.tau.ac.il/results/1240766462/treeView.html<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L 5 H,I,L,R,V <br />
51 A 9 A,Q,S <br />
52 T 9 A,T <br />
53 V 8 I,V <br />
54 Y 9 Y <br />
55 N 8 D,N,R <br />
56 T 8 N,T,V,X <br />
57 L 9 L <br />
58 N 7 H,K,N,R,T <br />
59 Q 7 A,L,Q,V <br />
60 L 7 F,L,M <br />
61 T 5 A,D,E,K,R,T <br />
62 D 4 A,D,E,Q,R,S <br />
63 A 7 A,I,M,S,V <br />
64 G 8 E,G,H <br />
65 L 6 I,L,M <br />
66 L 7 L,V <br />
67 R 4 I,K,L,Q,R,S,T,V <br />
68 Q 6 E,K,Q,R,S <br />
69 V 5 H,I,L,N,S,V <br />
70 S 5 D,H,N,P,Q,S,T <br />
71 V 5 F,L,P,V,Y <br />
72 D 2 A,D,E,G,S,T <br />
73 G 5 D,E,G,S,T <br />
74 T 5 A,D,G,N,S,T <br />
75 K 5 G,H,K,S,V <br />
76 T 6 A,K,S,T <br />
77 Y 6 H,I,K,R,V,Y <br />
78 F 6 F,Y <br />
79 D 8 D,E <br />
80 T 6 F,L,S,T <br />
81 N 3 A,D,N,R,S,T,V <br />
82 V 4* Q,V <br />
83 T 1 D,E,K,N,P,Q,T,V <br />
84 T 1 D,G,K,L,N,Q,S,T <br />
85 H 1 D,E,G,H,K,P,S <br />
86 H 8 D,E,H,N <br />
87 H 9 H <br />
88 Y 8 D,H,Y <br />
89 Y 9 H,Y <br />
90 L 2 A,I,L,M,V <br />
91 E 1 E,K,L,M,T,V <br />
92 N 2* D,E,K,N,Q,V <br />
93 S 7 C,S,T <br />
94 H 5 G,H,N,S <br />
95 E 6 E,K,T <br />
96 L 8 I,L,V <br />
97 V 6 F,I,T,V <br />
98 D 8 D,E <br />
99 I 8 F,I <br />
100 E 1 E,H,K,M,Q,S,T <br />
101 D 6 D,N,S,Y <br />
102 P 6 A,E,N,P <br />
103 H 1 D,E,G,H,I,Q,V <br />
104 L 8 I,L <br />
105 A 3* A,K,Q <br />
106 L 5* L,R <br />
107 S 7 Q,S <br />
108 K 3* D,K,R <br />
109 M 4* E,K,M <br />
110 P 7 I,P <br />
111 E 4* A,E,S,V <br />
112 V 2* A,E,R,V <br />
113 P 3* E,K,P,Q <br />
114 E 1 E,H,N,R,Y <br />
115 G 7 G,N <br />
116 Y 2 F,I,V,Y <br />
117 E 5* E,R <br />
118 I 6* I,L <br />
119 A 6* A,V <br />
120 R 4* D,R <br />
121 I 4* H,I <br />
122 D 6* D,N <br />
123 M 6* L,M <br />
124 V 8* V <br />
125 V 5* L,V <br />
126 R 4* R,Y <br />
127 L 6* L,V <br />
128 R 8* R <br />
129 K 8* K <br />
130 K 8* K <br />
131 R 6* K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Polar_regions/2'>Polar/Hydrophobic Regions</scene><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/N_to_c_rainbow/1'>Amino terminus to carboxy terminus</scene><br />
<br />
{{Template:ColorKey_Amino2CarboxyRainbow}}<br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
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<br />
<br />
<br />
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<br />
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<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
HOW WAS THE ANIMATED IMAGE GENERATED?<br />
<br />
1. Go to the POLYVIEW 3D homepage, http://polyview.cchmc.org/polyview3d.html<br />
<br />
2. On the submission form, first select 'animation' in the "type of request" section, select the size of the animation to be generated in pixels(here the size is 600), then upload the PDB format protein structure file in the "source of structural data" section.<br />
<br />
3. On the "chain color and rendering section" select 'cartoon' and 'secondary structure'.<br />
<br />
4. On "advanced structural annotation" section select 'docking models in Capri format'.<br />
<br />
5. Any other forms for the animation may be selected by referring to the "Samples" according to the protein structure to be animated.<br />
<br />
<br />
HOW WAS THE JMOL IMAGE GENERATED?<br />
<br />
1. First retrieve your protein sequence from http://www.ncbi.nlm.nih.gov/.<br />
<br />
2. Go to 3D-JIGSAW page http://bmm.cancerresearchuk.org/~3djigsaw/ and paste the sequence on the submission page. A .pdb format image of your protein will be sent to you on your email which can be opened by RASMOL.<br />
<br />
3. Upload this file on Proteopedia and then load the JMol applet for the protein following instructions on the Help:Editing page http://www.proteopedia.org/wiki/index.php/Help:Editing.<br />
<br />
4. You can edit your protein by using the scene authoring tools after loading the applet.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=953653User:Adam Meade/Sandbox 12009-05-04T22:57:08Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. To prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
=Phylogenetic Tree=<br />
<br />
http://consurf.tau.ac.il/results/1240766462/treeView.html<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L 5 H,I,L,R,V <br />
51 A 9 A,Q,S <br />
52 T 9 A,T <br />
53 V 8 I,V <br />
54 Y 9 Y <br />
55 N 8 D,N,R <br />
56 T 8 N,T,V,X <br />
57 L 9 L <br />
58 N 7 H,K,N,R,T <br />
59 Q 7 A,L,Q,V <br />
60 L 7 F,L,M <br />
61 T 5 A,D,E,K,R,T <br />
62 D 4 A,D,E,Q,R,S <br />
63 A 7 A,I,M,S,V <br />
64 G 8 E,G,H <br />
65 L 6 I,L,M <br />
66 L 7 L,V <br />
67 R 4 I,K,L,Q,R,S,T,V <br />
68 Q 6 E,K,Q,R,S <br />
69 V 5 H,I,L,N,S,V <br />
70 S 5 D,H,N,P,Q,S,T <br />
71 V 5 F,L,P,V,Y <br />
72 D 2 A,D,E,G,S,T <br />
73 G 5 D,E,G,S,T <br />
74 T 5 A,D,G,N,S,T <br />
75 K 5 G,H,K,S,V <br />
76 T 6 A,K,S,T <br />
77 Y 6 H,I,K,R,V,Y <br />
78 F 6 F,Y <br />
79 D 8 D,E <br />
80 T 6 F,L,S,T <br />
81 N 3 A,D,N,R,S,T,V <br />
82 V 4* Q,V <br />
83 T 1 D,E,K,N,P,Q,T,V <br />
84 T 1 D,G,K,L,N,Q,S,T <br />
85 H 1 D,E,G,H,K,P,S <br />
86 H 8 D,E,H,N <br />
87 H 9 H <br />
88 Y 8 D,H,Y <br />
89 Y 9 H,Y <br />
90 L 2 A,I,L,M,V <br />
91 E 1 E,K,L,M,T,V <br />
92 N 2* D,E,K,N,Q,V <br />
93 S 7 C,S,T <br />
94 H 5 G,H,N,S <br />
95 E 6 E,K,T <br />
96 L 8 I,L,V <br />
97 V 6 F,I,T,V <br />
98 D 8 D,E <br />
99 I 8 F,I <br />
100 E 1 E,H,K,M,Q,S,T <br />
101 D 6 D,N,S,Y <br />
102 P 6 A,E,N,P <br />
103 H 1 D,E,G,H,I,Q,V <br />
104 L 8 I,L <br />
105 A 3* A,K,Q <br />
106 L 5* L,R <br />
107 S 7 Q,S <br />
108 K 3* D,K,R <br />
109 M 4* E,K,M <br />
110 P 7 I,P <br />
111 E 4* A,E,S,V <br />
112 V 2* A,E,R,V <br />
113 P 3* E,K,P,Q <br />
114 E 1 E,H,N,R,Y <br />
115 G 7 G,N <br />
116 Y 2 F,I,V,Y <br />
117 E 5* E,R <br />
118 I 6* I,L <br />
119 A 6* A,V <br />
120 R 4* D,R <br />
121 I 4* H,I <br />
122 D 6* D,N <br />
123 M 6* L,M <br />
124 V 8* V <br />
125 V 5* L,V <br />
126 R 4* R,Y <br />
127 L 6* L,V <br />
128 R 8* R <br />
129 K 8* K <br />
130 K 8* K <br />
131 R 6* K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Polar_regions/2'>Polar/Hydrophobic Regions</scene><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/N_to_c_rainbow/1'>Amino terminus to carboxy terminus</scene><br />
<br />
{{Template:ColorKey_Amino2CarboxyRainbow}}<br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
HOW WAS THE ANIMATED IMAGE GENERATED?<br />
<br />
1. Go to the POLYVIEW 3D homepage, http://polyview.cchmc.org/polyview3d.html<br />
<br />
2. On the submission form, first select 'animation' in the "type of request" section, select the size of the animation to be generated in pixels(here the size is 600), then upload the PDB format protein structure file in the "source of structural data" section.<br />
<br />
3. On the "chain color and rendering section" select 'cartoon' and 'secondary structure'.<br />
<br />
4. On "advanced structural annotation" section select 'docking models in Capri format'.<br />
<br />
5. Any other forms for the animation may be selected by referring to the "Samples" according to the protein structure to be animated.<br />
<br />
<br />
HOW WAS THE JMOL IMAGE GENERATED?<br />
<br />
1. First retrieve your protein sequence from http://www.ncbi.nlm.nih.gov/.<br />
<br />
2. Go to 3D-JIGSAW page http://bmm.cancerresearchuk.org/~3djigsaw/ and paste the sequence on the submission page. A .pdb format image of your protein will be sent to you on your email which can be opened by RASMOL.<br />
<br />
3. Upload this file on Proteopedia and then load the JMol applet for the protein following instructions on the Help:Editing page http://www.proteopedia.org/wiki/index.php/Help:Editing.<br />
<br />
4. You can edit your protein by using the scene authoring tools after loading the applet.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951487User:Adam Meade/Sandbox 12009-04-27T22:22:26Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
=Phylogenetic Tree=<br />
<br />
http://consurf.tau.ac.il/results/1240766462/treeView.html<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L 5 H,I,L,R,V <br />
51 A 9 A,Q,S <br />
52 T 9 A,T <br />
53 V 8 I,V <br />
54 Y 9 Y <br />
55 N 8 D,N,R <br />
56 T 8 N,T,V,X <br />
57 L 9 L <br />
58 N 7 H,K,N,R,T <br />
59 Q 7 A,L,Q,V <br />
60 L 7 F,L,M <br />
61 T 5 A,D,E,K,R,T <br />
62 D 4 A,D,E,Q,R,S <br />
63 A 7 A,I,M,S,V <br />
64 G 8 E,G,H <br />
65 L 6 I,L,M <br />
66 L 7 L,V <br />
67 R 4 I,K,L,Q,R,S,T,V <br />
68 Q 6 E,K,Q,R,S <br />
69 V 5 H,I,L,N,S,V <br />
70 S 5 D,H,N,P,Q,S,T <br />
71 V 5 F,L,P,V,Y <br />
72 D 2 A,D,E,G,S,T <br />
73 G 5 D,E,G,S,T <br />
74 T 5 A,D,G,N,S,T <br />
75 K 5 G,H,K,S,V <br />
76 T 6 A,K,S,T <br />
77 Y 6 H,I,K,R,V,Y <br />
78 F 6 F,Y <br />
79 D 8 D,E <br />
80 T 6 F,L,S,T <br />
81 N 3 A,D,N,R,S,T,V <br />
82 V 4* Q,V <br />
83 T 1 D,E,K,N,P,Q,T,V <br />
84 T 1 D,G,K,L,N,Q,S,T <br />
85 H 1 D,E,G,H,K,P,S <br />
86 H 8 D,E,H,N <br />
87 H 9 H <br />
88 Y 8 D,H,Y <br />
89 Y 9 H,Y <br />
90 L 2 A,I,L,M,V <br />
91 E 1 E,K,L,M,T,V <br />
92 N 2* D,E,K,N,Q,V <br />
93 S 7 C,S,T <br />
94 H 5 G,H,N,S <br />
95 E 6 E,K,T <br />
96 L 8 I,L,V <br />
97 V 6 F,I,T,V <br />
98 D 8 D,E <br />
99 I 8 F,I <br />
100 E 1 E,H,K,M,Q,S,T <br />
101 D 6 D,N,S,Y <br />
102 P 6 A,E,N,P <br />
103 H 1 D,E,G,H,I,Q,V <br />
104 L 8 I,L <br />
105 A 3* A,K,Q <br />
106 L 5* L,R <br />
107 S 7 Q,S <br />
108 K 3* D,K,R <br />
109 M 4* E,K,M <br />
110 P 7 I,P <br />
111 E 4* A,E,S,V <br />
112 V 2* A,E,R,V <br />
113 P 3* E,K,P,Q <br />
114 E 1 E,H,N,R,Y <br />
115 G 7 G,N <br />
116 Y 2 F,I,V,Y <br />
117 E 5* E,R <br />
118 I 6* I,L <br />
119 A 6* A,V <br />
120 R 4* D,R <br />
121 I 4* H,I <br />
122 D 6* D,N <br />
123 M 6* L,M <br />
124 V 8* V <br />
125 V 5* L,V <br />
126 R 4* R,Y <br />
127 L 6* L,V <br />
128 R 8* R <br />
129 K 8* K <br />
130 K 8* K <br />
131 R 6* K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Polar_regions/2'>Polar/Hydrophobic Regions</scene><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/N_to_c_rainbow/1'>Amino terminus to carboxy terminus</scene><br />
<br />
{{Template:ColorKey_Amino2CarboxyRainbow}}<br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
HOW WAS THE ANIMATED IMAGE GENERATED?<br />
<br />
1. Go to the POLYVIEW 3D homepage, http://polyview.cchmc.org/polyview3d.html<br />
<br />
2. On the submission form, first select 'animation' in the "type of request" section, select the size of the animation to be generated in pixels(here the size is 600), then upload the PDB format protein structure file in the "source of structural data" section.<br />
<br />
3. On the "chain color and rendering section" select 'cartoon' and 'secondary structure'.<br />
<br />
4. On "advanced structural annotation" section select 'docking models in Capri format'.<br />
<br />
5. Any other forms for the animation may be selected by referring to the "Samples" according to the protein structure to be animated.<br />
<br />
<br />
HOW WAS THE JMOL IMAGE GENERATED?<br />
<br />
1. First retrieve your protein sequence from http://www.ncbi.nlm.nih.gov/.<br />
<br />
2. Go to 3D-JIGSAW page http://bmm.cancerresearchuk.org/~3djigsaw/ and paste the sequence on the submission page. A .pdb format image of your protein will be sent to you on your email which can be opened by RASMOL.<br />
<br />
3. Upload this file on Proteopedia and then load the JMol applet for the protein following instructions on the Help:Editing page http://www.proteopedia.org/wiki/index.php/Help:Editing.<br />
<br />
4. You can edit your protein by using the scene authoring tools after loading the applet.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951486User:Adam Meade/Sandbox 12009-04-27T22:15:54Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
=Phylogenetic Tree=<br />
<br />
http://consurf.tau.ac.il/results/1240766462/treeView.html<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L 5 H,I,L,R,V <br />
51 A 9 A,Q,S <br />
52 T 9 A,T <br />
53 V 8 I,V <br />
54 Y 9 Y <br />
55 N 8 D,N,R <br />
56 T 8 N,T,V,X <br />
57 L 9 L <br />
58 N 7 H,K,N,R,T <br />
59 Q 7 A,L,Q,V <br />
60 L 7 F,L,M <br />
61 T 5 A,D,E,K,R,T <br />
62 D 4 A,D,E,Q,R,S <br />
63 A 7 A,I,M,S,V <br />
64 G 8 E,G,H <br />
65 L 6 I,L,M <br />
66 L 7 L,V <br />
67 R 4 I,K,L,Q,R,S,T,V <br />
68 Q 6 E,K,Q,R,S <br />
69 V 5 H,I,L,N,S,V <br />
70 S 5 D,H,N,P,Q,S,T <br />
71 V 5 F,L,P,V,Y <br />
72 D 2 A,D,E,G,S,T <br />
73 G 5 D,E,G,S,T <br />
74 T 5 A,D,G,N,S,T <br />
75 K 5 G,H,K,S,V <br />
76 T 6 A,K,S,T <br />
77 Y 6 H,I,K,R,V,Y <br />
78 F 6 F,Y <br />
79 D 8 D,E <br />
80 T 6 F,L,S,T <br />
81 N 3 A,D,N,R,S,T,V <br />
82 V 4* Q,V <br />
83 T 1 D,E,K,N,P,Q,T,V <br />
84 T 1 D,G,K,L,N,Q,S,T <br />
85 H 1 D,E,G,H,K,P,S <br />
86 H 8 D,E,H,N <br />
87 H 9 H <br />
88 Y 8 D,H,Y <br />
89 Y 9 H,Y <br />
90 L 2 A,I,L,M,V <br />
91 E 1 E,K,L,M,T,V <br />
92 N 2* D,E,K,N,Q,V <br />
93 S 7 C,S,T <br />
94 H 5 G,H,N,S <br />
95 E 6 E,K,T <br />
96 L 8 I,L,V <br />
97 V 6 F,I,T,V <br />
98 D 8 D,E <br />
99 I 8 F,I <br />
100 E 1 E,H,K,M,Q,S,T <br />
101 D 6 D,N,S,Y <br />
102 P 6 A,E,N,P <br />
103 H 1 D,E,G,H,I,Q,V <br />
104 L 8 I,L <br />
105 A 3* A,K,Q <br />
106 L 5* L,R <br />
107 S 7 Q,S <br />
108 K 3* D,K,R <br />
109 M 4* E,K,M <br />
110 P 7 I,P <br />
111 E 4* A,E,S,V <br />
112 V 2* A,E,R,V <br />
113 P 3* E,K,P,Q <br />
114 E 1 E,H,N,R,Y <br />
115 G 7 G,N <br />
116 Y 2 F,I,V,Y <br />
117 E 5* E,R <br />
118 I 6* I,L <br />
119 A 6* A,V <br />
120 R 4* D,R <br />
121 I 4* H,I <br />
122 D 6* D,N <br />
123 M 6* L,M <br />
124 V 8* V <br />
125 V 5* L,V <br />
126 R 4* R,Y <br />
127 L 6* L,V <br />
128 R 8* R <br />
129 K 8* K <br />
130 K 8* K <br />
131 R 6* K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Polar_regions/2'>Polar/Hydrophobic Regions</scene><br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
HOW WAS THE ANIMATED IMAGE GENERATED?<br />
<br />
1. Go to the POLYVIEW 3D homepage, http://polyview.cchmc.org/polyview3d.html<br />
<br />
2. On the submission form, first select 'animation' in the "type of request" section, select the size of the animation to be generated in pixels(here the size is 600), then upload the PDB format protein structure file in the "source of structural data" section.<br />
<br />
3. On the "chain color and rendering section" select 'cartoon' and 'secondary structure'.<br />
<br />
4. On "advanced structural annotation" section select 'docking models in Capri format'.<br />
<br />
5. Any other forms for the animation may be selected by referring to the "Samples" according to the protein structure to be animated.<br />
<br />
<br />
HOW WAS THE JMOL IMAGE GENERATED?<br />
<br />
1. First retrieve your protein sequence from http://www.ncbi.nlm.nih.gov/.<br />
<br />
2. Go to 3D-JIGSAW page http://bmm.cancerresearchuk.org/~3djigsaw/ and paste the sequence on the submission page. A .pdb format image of your protein will be sent to you on your email which can be opened by RASMOL.<br />
<br />
3. Upload this file on Proteopedia and then load the JMol applet for the protein following instructions on the Help:Editing page http://www.proteopedia.org/wiki/index.php/Help:Editing.<br />
<br />
4. You can edit your protein by using the scene authoring tools after loading the applet.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951485User:Adam Meade/Sandbox 12009-04-27T22:12:23Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
=Phylogenetic Tree=<br />
<br />
http://consurf.tau.ac.il/results/1240766462/treeView.html<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L 5 H,I,L,R,V <br />
51 A 9 A,Q,S <br />
52 T 9 A,T <br />
53 V 8 I,V <br />
54 Y 9 Y <br />
55 N 8 D,N,R <br />
56 T 8 N,T,V,X <br />
57 L 9 L <br />
58 N 7 H,K,N,R,T <br />
59 Q 7 A,L,Q,V <br />
60 L 7 F,L,M <br />
61 T 5 A,D,E,K,R,T <br />
62 D 4 A,D,E,Q,R,S <br />
63 A 7 A,I,M,S,V <br />
64 G 8 E,G,H <br />
65 L 6 I,L,M <br />
66 L 7 L,V <br />
67 R 4 I,K,L,Q,R,S,T,V <br />
68 Q 6 E,K,Q,R,S <br />
69 V 5 H,I,L,N,S,V <br />
70 S 5 D,H,N,P,Q,S,T <br />
71 V 5 F,L,P,V,Y <br />
72 D 2 A,D,E,G,S,T <br />
73 G 5 D,E,G,S,T <br />
74 T 5 A,D,G,N,S,T <br />
75 K 5 G,H,K,S,V <br />
76 T 6 A,K,S,T <br />
77 Y 6 H,I,K,R,V,Y <br />
78 F 6 F,Y <br />
79 D 8 D,E <br />
80 T 6 F,L,S,T <br />
81 N 3 A,D,N,R,S,T,V <br />
82 V 4* Q,V <br />
83 T 1 D,E,K,N,P,Q,T,V <br />
84 T 1 D,G,K,L,N,Q,S,T <br />
85 H 1 D,E,G,H,K,P,S <br />
86 H 8 D,E,H,N <br />
87 H 9 H <br />
88 Y 8 D,H,Y <br />
89 Y 9 H,Y <br />
90 L 2 A,I,L,M,V <br />
91 E 1 E,K,L,M,T,V <br />
92 N 2* D,E,K,N,Q,V <br />
93 S 7 C,S,T <br />
94 H 5 G,H,N,S <br />
95 E 6 E,K,T <br />
96 L 8 I,L,V <br />
97 V 6 F,I,T,V <br />
98 D 8 D,E <br />
99 I 8 F,I <br />
100 E 1 E,H,K,M,Q,S,T <br />
101 D 6 D,N,S,Y <br />
102 P 6 A,E,N,P <br />
103 H 1 D,E,G,H,I,Q,V <br />
104 L 8 I,L <br />
105 A 3* A,K,Q <br />
106 L 5* L,R <br />
107 S 7 Q,S <br />
108 K 3* D,K,R <br />
109 M 4* E,K,M <br />
110 P 7 I,P <br />
111 E 4* A,E,S,V <br />
112 V 2* A,E,R,V <br />
113 P 3* E,K,P,Q <br />
114 E 1 E,H,N,R,Y <br />
115 G 7 G,N <br />
116 Y 2 F,I,V,Y <br />
117 E 5* E,R <br />
118 I 6* I,L <br />
119 A 6* A,V <br />
120 R 4* D,R <br />
121 I 4* H,I <br />
122 D 6* D,N <br />
123 M 6* L,M <br />
124 V 8* V <br />
125 V 5* L,V <br />
126 R 4* R,Y <br />
127 L 6* L,V <br />
128 R 8* R <br />
129 K 8* K <br />
130 K 8* K <br />
131 R 6* K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Polar_regions/1'>Polar/Hydrophobic regions</scene><br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
HOW WAS THE ANIMATED IMAGE GENERATED?<br />
<br />
1. Go to the POLYVIEW 3D homepage, http://polyview.cchmc.org/polyview3d.html<br />
<br />
2. On the submission form, first select 'animation' in the "type of request" section, select the size of the animation to be generated in pixels(here the size is 600), then upload the PDB format protein structure file in the "source of structural data" section.<br />
<br />
3. On the "chain color and rendering section" select 'cartoon' and 'secondary structure'.<br />
<br />
4. On "advanced structural annotation" section select 'docking models in Capri format'.<br />
<br />
5. Any other forms for the animation may be selected by referring to the "Samples" according to the protein structure to be animated.<br />
<br />
<br />
HOW WAS THE JMOL IMAGE GENERATED?<br />
<br />
1. First retrieve your protein sequence from http://www.ncbi.nlm.nih.gov/.<br />
<br />
2. Go to 3D-JIGSAW page http://bmm.cancerresearchuk.org/~3djigsaw/ and paste the sequence on the submission page. A .pdb format image of your protein will be sent to you on your email which can be opened by RASMOL.<br />
<br />
3. Upload this file on Proteopedia and then load the JMol applet for the protein following instructions on the Help:Editing page http://www.proteopedia.org/wiki/index.php/Help:Editing.<br />
<br />
4. You can edit your protein by using the scene authoring tools after loading the applet.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951484User:Adam Meade/Sandbox 12009-04-27T22:07:46Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
=Phylogenetic Tree=<br />
<br />
http://consurf.tau.ac.il/results/1240766462/treeView.html<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L 5 H,I,L,R,V <br />
51 A 9 A,Q,S <br />
52 T 9 A,T <br />
53 V 8 I,V <br />
54 Y 9 Y <br />
55 N 8 D,N,R <br />
56 T 8 N,T,V,X <br />
57 L 9 L <br />
58 N 7 H,K,N,R,T <br />
59 Q 7 A,L,Q,V <br />
60 L 7 F,L,M <br />
61 T 5 A,D,E,K,R,T <br />
62 D 4 A,D,E,Q,R,S <br />
63 A 7 A,I,M,S,V <br />
64 G 8 E,G,H <br />
65 L 6 I,L,M <br />
66 L 7 L,V <br />
67 R 4 I,K,L,Q,R,S,T,V <br />
68 Q 6 E,K,Q,R,S <br />
69 V 5 H,I,L,N,S,V <br />
70 S 5 D,H,N,P,Q,S,T <br />
71 V 5 F,L,P,V,Y <br />
72 D 2 A,D,E,G,S,T <br />
73 G 5 D,E,G,S,T <br />
74 T 5 A,D,G,N,S,T <br />
75 K 5 G,H,K,S,V <br />
76 T 6 A,K,S,T <br />
77 Y 6 H,I,K,R,V,Y <br />
78 F 6 F,Y <br />
79 D 8 D,E <br />
80 T 6 F,L,S,T <br />
81 N 3 A,D,N,R,S,T,V <br />
82 V 4* Q,V <br />
83 T 1 D,E,K,N,P,Q,T,V <br />
84 T 1 D,G,K,L,N,Q,S,T <br />
85 H 1 D,E,G,H,K,P,S <br />
86 H 8 D,E,H,N <br />
87 H 9 H <br />
88 Y 8 D,H,Y <br />
89 Y 9 H,Y <br />
90 L 2 A,I,L,M,V <br />
91 E 1 E,K,L,M,T,V <br />
92 N 2* D,E,K,N,Q,V <br />
93 S 7 C,S,T <br />
94 H 5 G,H,N,S <br />
95 E 6 E,K,T <br />
96 L 8 I,L,V <br />
97 V 6 F,I,T,V <br />
98 D 8 D,E <br />
99 I 8 F,I <br />
100 E 1 E,H,K,M,Q,S,T <br />
101 D 6 D,N,S,Y <br />
102 P 6 A,E,N,P <br />
103 H 1 D,E,G,H,I,Q,V <br />
104 L 8 I,L <br />
105 A 3* A,K,Q <br />
106 L 5* L,R <br />
107 S 7 Q,S <br />
108 K 3* D,K,R <br />
109 M 4* E,K,M <br />
110 P 7 I,P <br />
111 E 4* A,E,S,V <br />
112 V 2* A,E,R,V <br />
113 P 3* E,K,P,Q <br />
114 E 1 E,H,N,R,Y <br />
115 G 7 G,N <br />
116 Y 2 F,I,V,Y <br />
117 E 5* E,R <br />
118 I 6* I,L <br />
119 A 6* A,V <br />
120 R 4* D,R <br />
121 I 4* H,I <br />
122 D 6* D,N <br />
123 M 6* L,M <br />
124 V 8* V <br />
125 V 5* L,V <br />
126 R 4* R,Y <br />
127 L 6* L,V <br />
128 R 8* R <br />
129 K 8* K <br />
130 K 8* K <br />
131 R 6* K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
HOW WAS THE ANIMATED IMAGE GENERATED?<br />
<br />
1. Go to the POLYVIEW 3D homepage, http://polyview.cchmc.org/polyview3d.html<br />
<br />
2. On the submission form, first select 'animation' in the "type of request" section, select the size of the animation to be generated in pixels(here the size is 600), then upload the PDB format protein structure file in the "source of structural data" section.<br />
<br />
3. On the "chain color and rendering section" select 'cartoon' and 'secondary structure'.<br />
<br />
4. On "advanced structural annotation" section select 'docking models in Capri format'.<br />
<br />
5. Any other forms for the animation may be selected by referring to the "Samples" according to the protein structure to be animated.<br />
<br />
<br />
HOW WAS THE JMOL IMAGE GENERATED?<br />
<br />
1. First retrieve your protein sequence from http://www.ncbi.nlm.nih.gov/.<br />
<br />
2. Go to 3D-JIGSAW page http://bmm.cancerresearchuk.org/~3djigsaw/ and paste the sequence on the submission page. A .pdb format image of your protein will be sent to you on your email which can be opened by RASMOL.<br />
<br />
3. Upload this file on Proteopedia and then load the JMol applet for the protein following instructions on the Help:Editing page http://www.proteopedia.org/wiki/index.php/Help:Editing.<br />
<br />
4. You can edit your protein by using the scene authoring tools after loading the applet.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951483User:Adam Meade/Sandbox 12009-04-27T22:03:18Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L 5 H,I,L,R,V <br />
51 A 9 A,Q,S <br />
52 T 9 A,T <br />
53 V 8 I,V <br />
54 Y 9 Y <br />
55 N 8 D,N,R <br />
56 T 8 N,T,V,X <br />
57 L 9 L <br />
58 N 7 H,K,N,R,T <br />
59 Q 7 A,L,Q,V <br />
60 L 7 F,L,M <br />
61 T 5 A,D,E,K,R,T <br />
62 D 4 A,D,E,Q,R,S <br />
63 A 7 A,I,M,S,V <br />
64 G 8 E,G,H <br />
65 L 6 I,L,M <br />
66 L 7 L,V <br />
67 R 4 I,K,L,Q,R,S,T,V <br />
68 Q 6 E,K,Q,R,S <br />
69 V 5 H,I,L,N,S,V <br />
70 S 5 D,H,N,P,Q,S,T <br />
71 V 5 F,L,P,V,Y <br />
72 D 2 A,D,E,G,S,T <br />
73 G 5 D,E,G,S,T <br />
74 T 5 A,D,G,N,S,T <br />
75 K 5 G,H,K,S,V <br />
76 T 6 A,K,S,T <br />
77 Y 6 H,I,K,R,V,Y <br />
78 F 6 F,Y <br />
79 D 8 D,E <br />
80 T 6 F,L,S,T <br />
81 N 3 A,D,N,R,S,T,V <br />
82 V 4* Q,V <br />
83 T 1 D,E,K,N,P,Q,T,V <br />
84 T 1 D,G,K,L,N,Q,S,T <br />
85 H 1 D,E,G,H,K,P,S <br />
86 H 8 D,E,H,N <br />
87 H 9 H <br />
88 Y 8 D,H,Y <br />
89 Y 9 H,Y <br />
90 L 2 A,I,L,M,V <br />
91 E 1 E,K,L,M,T,V <br />
92 N 2* D,E,K,N,Q,V <br />
93 S 7 C,S,T <br />
94 H 5 G,H,N,S <br />
95 E 6 E,K,T <br />
96 L 8 I,L,V <br />
97 V 6 F,I,T,V <br />
98 D 8 D,E <br />
99 I 8 F,I <br />
100 E 1 E,H,K,M,Q,S,T <br />
101 D 6 D,N,S,Y <br />
102 P 6 A,E,N,P <br />
103 H 1 D,E,G,H,I,Q,V <br />
104 L 8 I,L <br />
105 A 3* A,K,Q <br />
106 L 5* L,R <br />
107 S 7 Q,S <br />
108 K 3* D,K,R <br />
109 M 4* E,K,M <br />
110 P 7 I,P <br />
111 E 4* A,E,S,V <br />
112 V 2* A,E,R,V <br />
113 P 3* E,K,P,Q <br />
114 E 1 E,H,N,R,Y <br />
115 G 7 G,N <br />
116 Y 2 F,I,V,Y <br />
117 E 5* E,R <br />
118 I 6* I,L <br />
119 A 6* A,V <br />
120 R 4* D,R <br />
121 I 4* H,I <br />
122 D 6* D,N <br />
123 M 6* L,M <br />
124 V 8* V <br />
125 V 5* L,V <br />
126 R 4* R,Y <br />
127 L 6* L,V <br />
128 R 8* R <br />
129 K 8* K <br />
130 K 8* K <br />
131 R 6* K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/><br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
HOW WAS THE ANIMATED IMAGE GENERATED?<br />
<br />
1. Go to the POLYVIEW 3D homepage, http://polyview.cchmc.org/polyview3d.html<br />
<br />
2. On the submission form, first select 'animation' in the "type of request" section, select the size of the animation to be generated in pixels(here the size is 600), then upload the PDB format protein structure file in the "source of structural data" section.<br />
<br />
3. On the "chain color and rendering section" select 'cartoon' and 'secondary structure'.<br />
<br />
4. On "advanced structural annotation" section select 'docking models in Capri format'.<br />
<br />
5. Any other forms for the animation may be selected by referring to the "Samples" according to the protein structure to be animated.<br />
<br />
<br />
HOW WAS THE JMOL IMAGE GENERATED?<br />
<br />
1. First retrieve your protein sequence from http://www.ncbi.nlm.nih.gov/.<br />
<br />
2. Go to 3D-JIGSAW page http://bmm.cancerresearchuk.org/~3djigsaw/ and paste the sequence on the submission page. A .pdb format image of your protein will be sent to you on your email which can be opened by RASMOL.<br />
<br />
3. Upload this file on Proteopedia and then load the JMol applet for the protein following instructions on the Help:Editing page http://www.proteopedia.org/wiki/index.php/Help:Editing.<br />
<br />
4. You can edit your protein by using the scene authoring tools after loading the applet.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951481User:Adam Meade/Sandbox 12009-04-27T22:00:46Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L 5 H,I,L,R,V <br />
51 A 9 A,Q,S <br />
52 T 9 A,T <br />
53 V 8 I,V <br />
54 Y 9 Y <br />
55 N 8 D,N,R <br />
56 T 8 N,T,V,X <br />
57 L 9 L <br />
58 N 7 H,K,N,R,T <br />
59 Q 7 A,L,Q,V <br />
60 L 7 F,L,M <br />
61 T 5 A,D,E,K,R,T <br />
62 D 4 A,D,E,Q,R,S <br />
63 A 7 A,I,M,S,V <br />
64 G 8 E,G,H <br />
65 L 6 I,L,M <br />
66 L 7 L,V <br />
67 R 4 I,K,L,Q,R,S,T,V <br />
68 Q 6 E,K,Q,R,S <br />
69 V 5 H,I,L,N,S,V <br />
70 S 5 D,H,N,P,Q,S,T <br />
71 V 5 F,L,P,V,Y <br />
72 D 2 A,D,E,G,S,T <br />
73 G 5 D,E,G,S,T <br />
74 T 5 A,D,G,N,S,T <br />
75 K 5 G,H,K,S,V <br />
76 T 6 A,K,S,T <br />
77 Y 6 H,I,K,R,V,Y <br />
78 F 6 F,Y <br />
79 D 8 D,E <br />
80 T 6 F,L,S,T <br />
81 N 3 A,D,N,R,S,T,V <br />
82 V 4* Q,V <br />
83 T 1 D,E,K,N,P,Q,T,V <br />
84 T 1 D,G,K,L,N,Q,S,T <br />
85 H 1 D,E,G,H,K,P,S <br />
86 H 8 D,E,H,N <br />
87 H 9 H <br />
88 Y 8 D,H,Y <br />
89 Y 9 H,Y <br />
90 L 2 A,I,L,M,V <br />
91 E 1 E,K,L,M,T,V <br />
92 N 2* D,E,K,N,Q,V <br />
93 S 7 C,S,T <br />
94 H 5 G,H,N,S <br />
95 E 6 E,K,T <br />
96 L 8 I,L,V <br />
97 V 6 F,I,T,V <br />
98 D 8 D,E <br />
99 I 8 F,I <br />
100 E 1 E,H,K,M,Q,S,T <br />
101 D 6 D,N,S,Y <br />
102 P 6 A,E,N,P <br />
103 H 1 D,E,G,H,I,Q,V <br />
104 L 8 I,L <br />
105 A 3* A,K,Q <br />
106 L 5* L,R <br />
107 S 7 Q,S <br />
108 K 3* D,K,R <br />
109 M 4* E,K,M <br />
110 P 7 I,P <br />
111 E 4* A,E,S,V <br />
112 V 2* A,E,R,V <br />
113 P 3* E,K,P,Q <br />
114 E 1 E,H,N,R,Y <br />
115 G 7 G,N <br />
116 Y 2 F,I,V,Y <br />
117 E 5* E,R <br />
118 I 6* I,L <br />
119 A 6* A,V <br />
120 R 4* D,R <br />
121 I 4* H,I <br />
122 D 6* D,N <br />
123 M 6* L,M <br />
124 V 8* V <br />
125 V 5* L,V <br />
126 R 4* R,Y <br />
127 L 6* L,V <br />
128 R 8* R <br />
129 K 8* K <br />
130 K 8* K <br />
131 R 6* K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/></div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951480User:Adam Meade/Sandbox 12009-04-27T21:59:59Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- 3LATOM: The ATOM derived sequence in three letter code, including the AA's positions as they appear in the PDB file and the chain identifier.<br />
<br />
- SCORE: The normalized conservation scores.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- CONFIDENCE INTERVAL: When using the bayesian method for calculating rates, a confidence interval is assigned to each of the inferred evolutionary conservation scores.<br />
<br />
- CONFIDENCE INTERVAL COLORS: When using the bayesian method for calculating rates. The color scale representing the lower and upper bounds of the confidence interval.<br />
<br />
- MSA DATA: The number of aligned sequences having an amino acid (non-gapped) from the overall number of sequences at each position.<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L 5 H,I,L,R,V <br />
51 A 9 A,Q,S <br />
52 T 9 A,T <br />
53 V 8 I,V <br />
54 Y 9 Y <br />
55 N 8 D,N,R <br />
56 T 8 N,T,V,X <br />
57 L 9 L <br />
58 N 7 H,K,N,R,T <br />
59 Q 7 A,L,Q,V <br />
60 L 7 F,L,M <br />
61 T 5 A,D,E,K,R,T <br />
62 D 4 A,D,E,Q,R,S <br />
63 A 7 A,I,M,S,V <br />
64 G 8 E,G,H <br />
65 L 6 I,L,M <br />
66 L 7 L,V <br />
67 R 4 I,K,L,Q,R,S,T,V <br />
68 Q 6 E,K,Q,R,S <br />
69 V 5 H,I,L,N,S,V <br />
70 S 5 D,H,N,P,Q,S,T <br />
71 V 5 F,L,P,V,Y <br />
72 D 2 A,D,E,G,S,T <br />
73 G 5 D,E,G,S,T <br />
74 T 5 A,D,G,N,S,T <br />
75 K 5 G,H,K,S,V <br />
76 T 6 A,K,S,T <br />
77 Y 6 H,I,K,R,V,Y <br />
78 F 6 F,Y <br />
79 D 8 D,E <br />
80 T 6 F,L,S,T <br />
81 N 3 A,D,N,R,S,T,V <br />
82 V 4* Q,V <br />
83 T 1 D,E,K,N,P,Q,T,V <br />
84 T 1 D,G,K,L,N,Q,S,T <br />
85 H 1 D,E,G,H,K,P,S <br />
86 H 8 D,E,H,N <br />
87 H 9 H <br />
88 Y 8 D,H,Y <br />
89 Y 9 H,Y <br />
90 L 2 A,I,L,M,V <br />
91 E 1 E,K,L,M,T,V <br />
92 N 2* D,E,K,N,Q,V <br />
93 S 7 C,S,T <br />
94 H 5 G,H,N,S <br />
95 E 6 E,K,T <br />
96 L 8 I,L,V <br />
97 V 6 F,I,T,V <br />
98 D 8 D,E <br />
99 I 8 F,I <br />
100 E 1 E,H,K,M,Q,S,T <br />
101 D 6 D,N,S,Y <br />
102 P 6 A,E,N,P <br />
103 H 1 D,E,G,H,I,Q,V <br />
104 L 8 I,L <br />
105 A 3* A,K,Q <br />
106 L 5* L,R <br />
107 S 7 Q,S <br />
108 K 3* D,K,R <br />
109 M 4* E,K,M <br />
110 P 7 I,P <br />
111 E 4* A,E,S,V <br />
112 V 2* A,E,R,V <br />
113 P 3* E,K,P,Q <br />
114 E 1 E,H,N,R,Y <br />
115 G 7 G,N <br />
116 Y 2 F,I,V,Y <br />
117 E 5* E,R <br />
118 I 6* I,L <br />
119 A 6* A,V <br />
120 R 4* D,R <br />
121 I 4* H,I <br />
122 D 6* D,N <br />
123 M 6* L,M <br />
124 V 8* V <br />
125 V 5* L,V <br />
126 R 4* R,Y <br />
127 L 6* L,V <br />
128 R 8* R <br />
129 K 8* K <br />
130 K 8* K <br />
131 R 6* K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/></div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951478User:Adam Meade/Sandbox 12009-04-27T21:53:31Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- 3LATOM: The ATOM derived sequence in three letter code, including the AA's positions as they appear in the PDB file and the chain identifier.<br />
<br />
- SCORE: The normalized conservation scores.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- CONFIDENCE INTERVAL: When using the bayesian method for calculating rates, a confidence interval is assigned to each of the inferred evolutionary conservation scores.<br />
<br />
- CONFIDENCE INTERVAL COLORS: When using the bayesian method for calculating rates. The color scale representing the lower and upper bounds of the confidence interval.<br />
<br />
- MSA DATA: The number of aligned sequences having an amino acid (non-gapped) from the overall number of sequences at each position.<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L 5 H,I,L,R,V <br />
51 A 9 A,Q,S <br />
52 T 9 A,T <br />
53 V 8 I,V <br />
54 Y 9 Y <br />
55 N 8 D,N,R <br />
56 T 8 N,T,V,X <br />
57 L 9 L <br />
58 N 7 H,K,N,R,T <br />
59 Q 7 A,L,Q,V <br />
60 L 7 F,L,M <br />
61 T 5 A,D,E,K,R,T <br />
62 D 4 A,D,E,Q,R,S <br />
63 A 7 A,I,M,S,V <br />
64 G 8 E,G,H <br />
65 L 6 I,L,M <br />
66 L 7 L,V <br />
67 R 4 I,K,L,Q,R,S,T,V <br />
68 Q 6 E,K,Q,R,S <br />
69 V 5 H,I,L,N,S,V <br />
70 S 5 D,H,N,P,Q,S,T <br />
71 V 5 F,L,P,V,Y <br />
72 D 2 A,D,E,G,S,T <br />
73 G 5 D,E,G,S,T <br />
74 T 5 A,D,G,N,S,T <br />
75 K 5 G,H,K,S,V <br />
76 T 6 A,K,S,T <br />
77 Y 6 H,I,K,R,V,Y <br />
78 F 6 F,Y <br />
79 D 8 D,E <br />
80 T 6 F,L,S,T <br />
81 N 3 A,D,N,R,S,T,V <br />
82 V 4* Q,V <br />
83 T 1 D,E,K,N,P,Q,T,V <br />
84 T 1 D,G,K,L,N,Q,S,T <br />
85 H 1 D,E,G,H,K,P,S <br />
86 H 8 D,E,H,N <br />
87 H 9 H <br />
88 Y 8 D,H,Y <br />
89 Y 9 H,Y <br />
90 L 2 A,I,L,M,V <br />
91 E 1 E,K,L,M,T,V <br />
92 N ASN124: 0.930 2* 0.016, 1.214 5,1 18/29 D,E,K,N,Q,V <br />
93 S SER125: -0.572 7 -0.986,-0.210 8,6 18/29 C,S,T <br />
94 H HIS126: -0.108 5 -0.721, 0.294 7,4 18/29 G,H,N,S <br />
95 E GLU127: -0.355 6 -0.859, 0.016 8,5 18/29 E,K,T <br />
96 L LEU128: -0.913 8 -1.223,-0.721 9,7 18/29 I,L,V <br />
97 V VAL129: -0.280 6 -0.721, 0.016 7,5 18/29 F,I,T,V <br />
98 D ASP130: -1.063 8 -1.338,-0.859 9,8 18/29 D,E <br />
99 I ILE131: -0.905 8 -1.223,-0.721 9,7 18/29 F,I <br />
100 E GLU132: 1.739 1 1.214, 2.633 1,1 18/29 E,H,K,M,Q,S,T <br />
101 D ASP133: -0.254 6 -0.721, 0.016 7,5 18/29 D,N,S,Y <br />
102 P PRO134: -0.193 6 -0.721, 0.294 7,4 18/29 A,E,N,P <br />
103 H HIS135: 1.561 1 0.661, 2.633 3,1 16/29 D,E,G,H,I,Q,V <br />
104 L LEU136: -1.023 8 -1.338,-0.859 9,8 16/29 I,L <br />
105 A ALA137: 0.666 3* -0.210, 1.214 6,1 7/29 A,K,Q <br />
106 L LEU138: 0.051 5* -0.721, 0.661 7,3 7/29 L,R <br />
107 S SER139: -0.624 7 -1.107,-0.210 8,6 7/29 Q,S <br />
108 K LYS140: 0.661 3* -0.210, 1.214 6,1 7/29 D,K,R <br />
109 M MET141: 0.164 4* -0.570, 0.661 7,3 7/29 E,K,M <br />
110 P PRO142: -0.492 7 -0.986,-0.210 8,6 7/29 I,P <br />
111 E GLU143: 0.243 4* -0.570, 0.661 7,3 7/29 A,E,S,V <br />
112 V VAL144: 0.835 2* 0.016, 1.214 5,1 7/29 A,E,R,V <br />
113 P PRO145: 0.779 3* 0.016, 1.214 5,1 7/29 E,K,P,Q <br />
114 E GLU146: 1.555 1 0.661, 2.633 3,1 7/29 E,H,N,R,Y <br />
115 G GLY147: -0.540 7 -1.107,-0.210 8,6 7/29 G,N <br />
116 Y TYR148: 1.072 2 0.294, 2.633 4,1 7/29 F,I,V,Y <br />
117 E GLU149: -0.017 5* -0.859, 0.661 8,3 5/29 E,R <br />
118 I ILE150: -0.332 6* -0.986, 0.016 8,5 5/29 I,L <br />
119 A ALA151: -0.318 6* -0.986, 0.016 8,5 3/29 A,V <br />
120 R ARG152: 0.307 4* -0.570, 1.214 7,1 3/29 D,R <br />
121 I ILE153: 0.330 4* -0.570, 1.214 7,1 3/29 H,I <br />
122 D ASP154: -0.429 6* -1.107, 0.016 8,5 3/29 D,N <br />
123 M MET155: -0.296 6* -0.986, 0.016 8,5 3/29 L,M <br />
124 V VAL156: -0.946 8* -1.455,-0.721 9,7 3/29 V <br />
125 V VAL157: -0.137 5* -0.859, 0.294 8,4 3/29 L,V <br />
126 R ARG158: 0.277 4* -0.570, 1.214 7,1 3/29 R,Y <br />
127 L LEU159: -0.174 6* -0.859, 0.294 8,4 3/29 L,V <br />
128 R ARG160: -0.959 8* -1.455,-0.721 9,7 3/29 R <br />
129 K LYS161: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
130 K LYS162: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
131 R ARG163: -0.419 6* -1.107, 0.016 8,5 3/29 K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/></div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951476User:Adam Meade/Sandbox 12009-04-27T21:46:35Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
<br />
<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- 3LATOM: The ATOM derived sequence in three letter code, including the AA's positions as they appear in the PDB file and the chain identifier.<br />
<br />
- SCORE: The normalized conservation scores.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- CONFIDENCE INTERVAL: When using the bayesian method for calculating rates, a confidence interval is assigned to each of the inferred evolutionary conservation scores.<br />
<br />
- CONFIDENCE INTERVAL COLORS: When using the bayesian method for calculating rates. The color scale representing the lower and upper bounds of the confidence interval.<br />
<br />
- MSA DATA: The number of aligned sequences having an amino acid (non-gapped) from the overall number of sequences at each position.<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ COLOR RESIDUE VARIETY<br />
(normalized) <br />
1 D 9 D <br />
2 V 2* F,N,V,Y <br />
3 N 6 A,N,S,T <br />
4 E 3* E,G,K,Q,S,T <br />
5 M 3* A,E,I,L,M,Q,T <br />
6 L 9 L <br />
7 Q 7 K,Q,R <br />
8 S 1 D,E,K,N,Q,R,S,T <br />
9 A 5 A,G,I,M,N,S,T,V <br />
10 G 8 D,G <br />
11 L 8 I,L,V <br />
12 R 8 K,R <br />
13 P 4 A,I,P,V,Y <br />
14 T 9 T <br />
15 R 3* E,F,G,K,L,P,R,V <br />
16 Q 8 P,Q <br />
17 R 9 R <br />
18 M 3* E,H,I,L,M,Q,V <br />
19 A 8 A,K,T,V <br />
20 L 7 I,L,V <br />
21 G 6 G,I,L,M <br />
22 W 1 A,D,E,K,N,Q,R,W <br />
23 L 1 A,F,I,L,M,T,V,Y <br />
24 L 7 F,L,M,V <br />
25 F 1 D,E,F,I,K,N,Q,R,V,Y<br />
26 G 1 A,E,G,H,K,N,Q,S,T <br />
27 K 3* A,E,H,K,P,S,T <br />
28 G 1 A,D,E,G,H,K,M,P,R <br />
29 A 1 A,C,E,G,L,M,N,Q,S,T<br />
30 R 1 E,H,Q,R <br />
31 H 9 H <br />
32 L 3* A,F,I,L,M,P,V,Y <br />
33 T 8 D,E,S,T <br />
34 A 9 A,P,T <br />
35 E 8 D,E <br />
36 M 3* A,D,E,H,M,S,T <br />
37 L 5 C,I,L,V <br />
38 Y 7 F,I,Y <br />
39 E 5 E,G,K,M,N,Q,R <br />
40 E 1 A,E,H,I,K,L,R <br />
41 A 6 A,F,I,L,V <br />
42 T 2 A,E,I,L,M,R,S,T <br />
43 L 1 A,D,E,F,G,L,N,P,S,V<br />
44 A 1 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K 1 D,F,G,H,K,L,N,S <br />
46 V 3* C,E,L,M,P,S,V <br />
47 P 4 D,E,N,P <br />
48 V 7 I,M,V <br />
49 S 9 G,S <br />
50 L LEU82: -0.133 5 -0.570, 0.294 7,4 29/29 H,I,L,R,V <br />
51 A ALA83: -1.171 9 -1.338,-0.986 9,8 29/29 A,Q,S <br />
52 T THR84: -1.376 9 -1.588,-1.223 9,9 29/29 A,T <br />
53 V VAL85: -1.007 8 -1.223,-0.859 9,8 29/29 I,V <br />
54 Y TYR86: -1.335 9 -1.588,-1.223 9,9 29/29 Y <br />
55 N ASN87: -1.123 8 -1.338,-0.986 9,8 29/29 D,N,R <br />
56 T THR88: -0.956 8 -1.223,-0.721 9,7 29/29 N,T,V,X <br />
57 L LEU89: -1.357 9 -1.588,-1.223 9,9 29/29 L <br />
58 N ASN90: -0.647 7 -0.986,-0.403 8,6 29/29 H,K,N,R,T <br />
59 Q GLN91: -0.558 7 -0.859,-0.210 8,6 29/29 A,L,Q,V <br />
60 L LEU92: -0.570 7 -0.986,-0.210 8,6 29/29 F,L,M <br />
61 T THR93: -0.099 5 -0.570, 0.294 7,4 29/29 A,D,E,K,R,T <br />
62 D ASP94: 0.354 4 -0.210, 0.661 6,3 29/29 A,D,E,Q,R,S <br />
63 A ALA95: -0.757 7 -1.107,-0.570 8,7 29/29 A,I,M,S,V <br />
64 G GLY96: -0.841 8 -1.223,-0.570 9,7 29/29 E,G,H <br />
65 L LEU97: -0.306 6 -0.721, 0.016 7,5 29/29 I,L,M <br />
66 L LEU98: -0.712 7 -0.986,-0.403 8,6 29/29 L,V <br />
67 R ARG99: 0.384 4 -0.210, 0.661 6,3 29/29 I,K,L,Q,R,S,T,V <br />
68 Q GLN100: -0.238 6 -0.570, 0.016 7,5 29/29 E,K,Q,R,S <br />
69 V VAL101: -0.147 5 -0.570, 0.294 7,4 29/29 H,I,L,N,S,V <br />
70 S SER102: 0.078 5 -0.403, 0.294 6,4 29/29 D,H,N,P,Q,S,T <br />
71 V VAL103: 0.145 5 -0.403, 0.661 6,3 29/29 F,L,P,V,Y <br />
72 D ASP104: 0.881 2 0.294, 1.214 4,1 29/29 A,D,E,G,S,T <br />
73 G GLY105: 0.110 5 -0.403, 0.661 6,3 29/29 D,E,G,S,T <br />
74 T THR106: -0.006 5 -0.403, 0.294 6,4 29/29 A,D,G,N,S,T <br />
75 K LYS107: 0.077 5 -0.403, 0.294 6,4 29/29 G,H,K,S,V <br />
76 T THR108: -0.179 6 -0.570, 0.016 7,5 29/29 A,K,S,T <br />
77 Y TYR109: -0.415 6 -0.721,-0.210 7,6 29/29 H,I,K,R,V,Y <br />
78 F PHE110: -0.368 6 -0.721, 0.016 7,5 29/29 F,Y <br />
79 D ASP111: -1.082 8 -1.338,-0.859 9,8 29/29 D,E <br />
80 T THR112: -0.448 6 -0.859,-0.210 8,6 29/29 F,L,S,T <br />
81 N ASN113: 0.772 3 0.294, 1.214 4,1 29/29 A,D,N,R,S,T,V <br />
82 V VAL114: 0.383 4* -0.570, 1.214 7,1 2/29 Q,V <br />
83 T THR115: 2.165 1 1.214, 2.633 1,1 23/29 D,E,K,N,P,Q,T,V <br />
84 T THR116: 1.506 1 0.661, 2.633 3,1 29/29 D,G,K,L,N,Q,S,T <br />
85 H HIS117: 1.472 1 0.661, 2.633 3,1 29/29 D,E,G,H,K,P,S <br />
86 H HIS118: -0.825 8 -1.107,-0.570 8,7 29/29 D,E,H,N <br />
87 H HIS119: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
88 Y TYR120: -0.874 8 -1.107,-0.721 8,7 29/29 D,H,Y <br />
89 Y TYR121: -1.329 9 -1.455,-1.223 9,9 29/29 H,Y <br />
90 L LEU122: 1.136 2 0.294, 1.214 4,1 25/29 A,I,L,M,V <br />
91 E GLU123: 1.417 1 0.661, 2.633 3,1 18/29 E,K,L,M,T,V <br />
92 N ASN124: 0.930 2* 0.016, 1.214 5,1 18/29 D,E,K,N,Q,V <br />
93 S SER125: -0.572 7 -0.986,-0.210 8,6 18/29 C,S,T <br />
94 H HIS126: -0.108 5 -0.721, 0.294 7,4 18/29 G,H,N,S <br />
95 E GLU127: -0.355 6 -0.859, 0.016 8,5 18/29 E,K,T <br />
96 L LEU128: -0.913 8 -1.223,-0.721 9,7 18/29 I,L,V <br />
97 V VAL129: -0.280 6 -0.721, 0.016 7,5 18/29 F,I,T,V <br />
98 D ASP130: -1.063 8 -1.338,-0.859 9,8 18/29 D,E <br />
99 I ILE131: -0.905 8 -1.223,-0.721 9,7 18/29 F,I <br />
100 E GLU132: 1.739 1 1.214, 2.633 1,1 18/29 E,H,K,M,Q,S,T <br />
101 D ASP133: -0.254 6 -0.721, 0.016 7,5 18/29 D,N,S,Y <br />
102 P PRO134: -0.193 6 -0.721, 0.294 7,4 18/29 A,E,N,P <br />
103 H HIS135: 1.561 1 0.661, 2.633 3,1 16/29 D,E,G,H,I,Q,V <br />
104 L LEU136: -1.023 8 -1.338,-0.859 9,8 16/29 I,L <br />
105 A ALA137: 0.666 3* -0.210, 1.214 6,1 7/29 A,K,Q <br />
106 L LEU138: 0.051 5* -0.721, 0.661 7,3 7/29 L,R <br />
107 S SER139: -0.624 7 -1.107,-0.210 8,6 7/29 Q,S <br />
108 K LYS140: 0.661 3* -0.210, 1.214 6,1 7/29 D,K,R <br />
109 M MET141: 0.164 4* -0.570, 0.661 7,3 7/29 E,K,M <br />
110 P PRO142: -0.492 7 -0.986,-0.210 8,6 7/29 I,P <br />
111 E GLU143: 0.243 4* -0.570, 0.661 7,3 7/29 A,E,S,V <br />
112 V VAL144: 0.835 2* 0.016, 1.214 5,1 7/29 A,E,R,V <br />
113 P PRO145: 0.779 3* 0.016, 1.214 5,1 7/29 E,K,P,Q <br />
114 E GLU146: 1.555 1 0.661, 2.633 3,1 7/29 E,H,N,R,Y <br />
115 G GLY147: -0.540 7 -1.107,-0.210 8,6 7/29 G,N <br />
116 Y TYR148: 1.072 2 0.294, 2.633 4,1 7/29 F,I,V,Y <br />
117 E GLU149: -0.017 5* -0.859, 0.661 8,3 5/29 E,R <br />
118 I ILE150: -0.332 6* -0.986, 0.016 8,5 5/29 I,L <br />
119 A ALA151: -0.318 6* -0.986, 0.016 8,5 3/29 A,V <br />
120 R ARG152: 0.307 4* -0.570, 1.214 7,1 3/29 D,R <br />
121 I ILE153: 0.330 4* -0.570, 1.214 7,1 3/29 H,I <br />
122 D ASP154: -0.429 6* -1.107, 0.016 8,5 3/29 D,N <br />
123 M MET155: -0.296 6* -0.986, 0.016 8,5 3/29 L,M <br />
124 V VAL156: -0.946 8* -1.455,-0.721 9,7 3/29 V <br />
125 V VAL157: -0.137 5* -0.859, 0.294 8,4 3/29 L,V <br />
126 R ARG158: 0.277 4* -0.570, 1.214 7,1 3/29 R,Y <br />
127 L LEU159: -0.174 6* -0.859, 0.294 8,4 3/29 L,V <br />
128 R ARG160: -0.959 8* -1.455,-0.721 9,7 3/29 R <br />
129 K LYS161: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
130 K LYS162: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
131 R ARG163: -0.419 6* -1.107, 0.016 8,5 3/29 K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/></div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951470User:Adam Meade/Sandbox 12009-04-27T21:34:03Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- 3LATOM: The ATOM derived sequence in three letter code, including the AA's positions as they appear in the PDB file and the chain identifier.<br />
<br />
- SCORE: The normalized conservation scores.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- CONFIDENCE INTERVAL: When using the bayesian method for calculating rates, a confidence interval is assigned to each of the inferred evolutionary conservation scores.<br />
<br />
- CONFIDENCE INTERVAL COLORS: When using the bayesian method for calculating rates. The color scale representing the lower and upper bounds of the confidence interval.<br />
<br />
- MSA DATA: The number of aligned sequences having an amino acid (non-gapped) from the overall number of sequences at each position.<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ 3LATOM SCORE COLOR CONFIDENCE INTERVAL CONFIDENCE INTERVAL COLORS MSA DATA RESIDUE VARIETY<br />
(normalized) <br />
1 D ASP33: -1.189 9 -1.455,-0.986 9,8 10/29 D <br />
2 V VAL34: 0.979 2* 0.016, 2.633 5,1 10/29 F,N,V,Y <br />
3 N ASN35: -0.318 6 -0.859, 0.016 8,5 14/29 A,N,S,T <br />
4 E GLU36: 0.737 3* 0.016, 1.214 5,1 19/29 E,G,K,Q,S,T <br />
5 M MET37: 0.793 3* 0.016, 1.214 5,1 19/29 A,E,I,L,M,Q,T <br />
6 L LEU38: -1.329 9 -1.588,-1.223 9,9 28/29 L <br />
7 Q GLN39: -0.531 7 -0.859,-0.210 8,6 28/29 K,Q,R <br />
8 S SER40: 2.423 1 2.633, 2.633 1,1 28/29 D,E,K,N,Q,R,S,T <br />
9 A ALA41: 0.058 5 -0.403, 0.294 6,4 28/29 A,G,I,M,N,S,T,V <br />
10 G GLY42: -1.069 8 -1.338,-0.859 9,8 28/29 D,G <br />
11 L LEU43: -0.850 8 -1.223,-0.570 9,7 28/29 I,L,V <br />
12 R ARG44: -0.998 8 -1.223,-0.859 9,8 28/29 K,R <br />
13 P PRO45: 0.305 4 -0.210, 0.661 6,3 28/29 A,I,P,V,Y <br />
14 T THR46: -1.473 9 -1.588,-1.455 9,9 28/29 T <br />
15 R ARG47: 0.816 3* 0.016, 1.214 5,1 28/29 E,F,G,K,L,P,R,V <br />
16 Q GLN48: -0.961 8 -1.223,-0.721 9,7 28/29 P,Q <br />
17 R ARG49: -1.426 9 -1.588,-1.338 9,9 28/29 R <br />
18 M MET50: 0.754 3* 0.016, 1.214 5,1 28/29 E,H,I,L,M,Q,V <br />
19 A ALA51: -0.901 8 -1.223,-0.721 9,7 28/29 A,K,T,V <br />
20 L LEU52: -0.710 7 -0.986,-0.403 8,6 28/29 I,L,V <br />
21 G GLY53: -0.370 6 -0.859, 0.016 8,5 28/29 G,I,L,M <br />
22 W TRP54: 1.698 1 1.214, 2.633 1,1 28/29 A,D,E,K,N,Q,R,W <br />
23 L LEU55: 1.226 1 0.661, 2.633 3,1 28/29 A,F,I,L,M,T,V,Y <br />
24 L LEU56: -0.594 7 -0.986,-0.210 8,6 28/29 F,L,M,V <br />
25 F PHE57: 1.556 1 0.661, 2.633 3,1 28/29 D,E,F,I,K,N,Q,R,V,Y<br />
26 G GLY58: 2.434 1 2.633, 2.633 1,1 28/29 A,E,G,H,K,N,Q,S,T <br />
27 K LYS59: 0.609 3* 0.016, 1.214 5,1 28/29 A,E,H,K,P,S,T <br />
28 G GLY60: 2.294 1 2.633, 2.633 1,1 29/29 A,D,E,G,H,K,M,P,R <br />
29 A ALA61: 2.262 1 2.633, 2.633 1,1 27/29 A,C,E,G,L,M,N,Q,S,T<br />
30 R ARG62: 1.468 1 0.661, 2.633 3,1 19/29 E,H,Q,R <br />
31 H HIS63: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
32 L LEU64: 0.771 3* 0.016, 1.214 5,1 29/29 A,F,I,L,M,P,V,Y <br />
33 T THR65: -0.874 8 -1.107,-0.721 8,7 29/29 D,E,S,T <br />
34 A ALA66: -1.188 9 -1.338,-0.986 9,8 29/29 A,P,T <br />
35 E GLU67: -1.035 8 -1.338,-0.859 9,8 29/29 D,E <br />
36 M MET68: 0.707 3* 0.016, 1.214 5,1 29/29 A,D,E,H,M,S,T <br />
37 L LEU69: 0.078 5 -0.403, 0.294 6,4 29/29 C,I,L,V <br />
38 Y TYR70: -0.574 7 -0.986,-0.210 8,6 29/29 F,I,Y <br />
39 E GLU71: 0.157 5 -0.403, 0.661 6,3 29/29 E,G,K,M,N,Q,R <br />
40 E GLU72: 1.498 1 0.661, 2.633 3,1 29/29 A,E,H,I,K,L,R <br />
41 A ALA73: -0.319 6 -0.721, 0.016 7,5 29/29 A,F,I,L,V <br />
42 T THR74: 1.036 2 0.294, 1.214 4,1 29/29 A,E,I,L,M,R,S,T <br />
43 L LEU75: 1.694 1 0.661, 2.633 3,1 29/29 A,D,E,F,G,L,N,P,S,V<br />
44 A ALA76: 2.302 1 2.633, 2.633 1,1 29/29 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K LYS77: 2.001 1 1.214, 2.633 1,1 29/29 D,F,G,H,K,L,N,S <br />
46 V VAL78: 0.670 3* 0.016, 1.214 5,1 29/29 C,E,L,M,P,S,V <br />
47 P PRO79: 0.328 4 -0.210, 0.661 6,3 29/29 D,E,N,P <br />
48 V VAL80: -0.744 7 -0.986,-0.570 8,7 29/29 I,M,V <br />
49 S SER81: -1.279 9 -1.455,-1.107 9,8 29/29 G,S <br />
50 L LEU82: -0.133 5 -0.570, 0.294 7,4 29/29 H,I,L,R,V <br />
51 A ALA83: -1.171 9 -1.338,-0.986 9,8 29/29 A,Q,S <br />
52 T THR84: -1.376 9 -1.588,-1.223 9,9 29/29 A,T <br />
53 V VAL85: -1.007 8 -1.223,-0.859 9,8 29/29 I,V <br />
54 Y TYR86: -1.335 9 -1.588,-1.223 9,9 29/29 Y <br />
55 N ASN87: -1.123 8 -1.338,-0.986 9,8 29/29 D,N,R <br />
56 T THR88: -0.956 8 -1.223,-0.721 9,7 29/29 N,T,V,X <br />
57 L LEU89: -1.357 9 -1.588,-1.223 9,9 29/29 L <br />
58 N ASN90: -0.647 7 -0.986,-0.403 8,6 29/29 H,K,N,R,T <br />
59 Q GLN91: -0.558 7 -0.859,-0.210 8,6 29/29 A,L,Q,V <br />
60 L LEU92: -0.570 7 -0.986,-0.210 8,6 29/29 F,L,M <br />
61 T THR93: -0.099 5 -0.570, 0.294 7,4 29/29 A,D,E,K,R,T <br />
62 D ASP94: 0.354 4 -0.210, 0.661 6,3 29/29 A,D,E,Q,R,S <br />
63 A ALA95: -0.757 7 -1.107,-0.570 8,7 29/29 A,I,M,S,V <br />
64 G GLY96: -0.841 8 -1.223,-0.570 9,7 29/29 E,G,H <br />
65 L LEU97: -0.306 6 -0.721, 0.016 7,5 29/29 I,L,M <br />
66 L LEU98: -0.712 7 -0.986,-0.403 8,6 29/29 L,V <br />
67 R ARG99: 0.384 4 -0.210, 0.661 6,3 29/29 I,K,L,Q,R,S,T,V <br />
68 Q GLN100: -0.238 6 -0.570, 0.016 7,5 29/29 E,K,Q,R,S <br />
69 V VAL101: -0.147 5 -0.570, 0.294 7,4 29/29 H,I,L,N,S,V <br />
70 S SER102: 0.078 5 -0.403, 0.294 6,4 29/29 D,H,N,P,Q,S,T <br />
71 V VAL103: 0.145 5 -0.403, 0.661 6,3 29/29 F,L,P,V,Y <br />
72 D ASP104: 0.881 2 0.294, 1.214 4,1 29/29 A,D,E,G,S,T <br />
73 G GLY105: 0.110 5 -0.403, 0.661 6,3 29/29 D,E,G,S,T <br />
74 T THR106: -0.006 5 -0.403, 0.294 6,4 29/29 A,D,G,N,S,T <br />
75 K LYS107: 0.077 5 -0.403, 0.294 6,4 29/29 G,H,K,S,V <br />
76 T THR108: -0.179 6 -0.570, 0.016 7,5 29/29 A,K,S,T <br />
77 Y TYR109: -0.415 6 -0.721,-0.210 7,6 29/29 H,I,K,R,V,Y <br />
78 F PHE110: -0.368 6 -0.721, 0.016 7,5 29/29 F,Y <br />
79 D ASP111: -1.082 8 -1.338,-0.859 9,8 29/29 D,E <br />
80 T THR112: -0.448 6 -0.859,-0.210 8,6 29/29 F,L,S,T <br />
81 N ASN113: 0.772 3 0.294, 1.214 4,1 29/29 A,D,N,R,S,T,V <br />
82 V VAL114: 0.383 4* -0.570, 1.214 7,1 2/29 Q,V <br />
83 T THR115: 2.165 1 1.214, 2.633 1,1 23/29 D,E,K,N,P,Q,T,V <br />
84 T THR116: 1.506 1 0.661, 2.633 3,1 29/29 D,G,K,L,N,Q,S,T <br />
85 H HIS117: 1.472 1 0.661, 2.633 3,1 29/29 D,E,G,H,K,P,S <br />
86 H HIS118: -0.825 8 -1.107,-0.570 8,7 29/29 D,E,H,N <br />
87 H HIS119: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
88 Y TYR120: -0.874 8 -1.107,-0.721 8,7 29/29 D,H,Y <br />
89 Y TYR121: -1.329 9 -1.455,-1.223 9,9 29/29 H,Y <br />
90 L LEU122: 1.136 2 0.294, 1.214 4,1 25/29 A,I,L,M,V <br />
91 E GLU123: 1.417 1 0.661, 2.633 3,1 18/29 E,K,L,M,T,V <br />
92 N ASN124: 0.930 2* 0.016, 1.214 5,1 18/29 D,E,K,N,Q,V <br />
93 S SER125: -0.572 7 -0.986,-0.210 8,6 18/29 C,S,T <br />
94 H HIS126: -0.108 5 -0.721, 0.294 7,4 18/29 G,H,N,S <br />
95 E GLU127: -0.355 6 -0.859, 0.016 8,5 18/29 E,K,T <br />
96 L LEU128: -0.913 8 -1.223,-0.721 9,7 18/29 I,L,V <br />
97 V VAL129: -0.280 6 -0.721, 0.016 7,5 18/29 F,I,T,V <br />
98 D ASP130: -1.063 8 -1.338,-0.859 9,8 18/29 D,E <br />
99 I ILE131: -0.905 8 -1.223,-0.721 9,7 18/29 F,I <br />
100 E GLU132: 1.739 1 1.214, 2.633 1,1 18/29 E,H,K,M,Q,S,T <br />
101 D ASP133: -0.254 6 -0.721, 0.016 7,5 18/29 D,N,S,Y <br />
102 P PRO134: -0.193 6 -0.721, 0.294 7,4 18/29 A,E,N,P <br />
103 H HIS135: 1.561 1 0.661, 2.633 3,1 16/29 D,E,G,H,I,Q,V <br />
104 L LEU136: -1.023 8 -1.338,-0.859 9,8 16/29 I,L <br />
105 A ALA137: 0.666 3* -0.210, 1.214 6,1 7/29 A,K,Q <br />
106 L LEU138: 0.051 5* -0.721, 0.661 7,3 7/29 L,R <br />
107 S SER139: -0.624 7 -1.107,-0.210 8,6 7/29 Q,S <br />
108 K LYS140: 0.661 3* -0.210, 1.214 6,1 7/29 D,K,R <br />
109 M MET141: 0.164 4* -0.570, 0.661 7,3 7/29 E,K,M <br />
110 P PRO142: -0.492 7 -0.986,-0.210 8,6 7/29 I,P <br />
111 E GLU143: 0.243 4* -0.570, 0.661 7,3 7/29 A,E,S,V <br />
112 V VAL144: 0.835 2* 0.016, 1.214 5,1 7/29 A,E,R,V <br />
113 P PRO145: 0.779 3* 0.016, 1.214 5,1 7/29 E,K,P,Q <br />
114 E GLU146: 1.555 1 0.661, 2.633 3,1 7/29 E,H,N,R,Y <br />
115 G GLY147: -0.540 7 -1.107,-0.210 8,6 7/29 G,N <br />
116 Y TYR148: 1.072 2 0.294, 2.633 4,1 7/29 F,I,V,Y <br />
117 E GLU149: -0.017 5* -0.859, 0.661 8,3 5/29 E,R <br />
118 I ILE150: -0.332 6* -0.986, 0.016 8,5 5/29 I,L <br />
119 A ALA151: -0.318 6* -0.986, 0.016 8,5 3/29 A,V <br />
120 R ARG152: 0.307 4* -0.570, 1.214 7,1 3/29 D,R <br />
121 I ILE153: 0.330 4* -0.570, 1.214 7,1 3/29 H,I <br />
122 D ASP154: -0.429 6* -1.107, 0.016 8,5 3/29 D,N <br />
123 M MET155: -0.296 6* -0.986, 0.016 8,5 3/29 L,M <br />
124 V VAL156: -0.946 8* -1.455,-0.721 9,7 3/29 V <br />
125 V VAL157: -0.137 5* -0.859, 0.294 8,4 3/29 L,V <br />
126 R ARG158: 0.277 4* -0.570, 1.214 7,1 3/29 R,Y <br />
127 L LEU159: -0.174 6* -0.859, 0.294 8,4 3/29 L,V <br />
128 R ARG160: -0.959 8* -1.455,-0.721 9,7 3/29 R <br />
129 K LYS161: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
130 K LYS162: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
131 R ARG163: -0.419 6* -1.107, 0.016 8,5 3/29 K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
=References=<br />
<references/></div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951423User:Adam Meade/Sandbox 12009-04-27T15:30:29Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
=Background Information=<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
=Irr and Other Iron-Regulating Proteins=<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Function of Irr=<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
=Chemical and Physical Properties of Irr=<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
=Evolution of Irr/Fur=<br />
<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- 3LATOM: The ATOM derived sequence in three letter code, including the AA's positions as they appear in the PDB file and the chain identifier.<br />
<br />
- SCORE: The normalized conservation scores.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- CONFIDENCE INTERVAL: When using the bayesian method for calculating rates, a confidence interval is assigned to each of the inferred evolutionary conservation scores.<br />
<br />
- CONFIDENCE INTERVAL COLORS: When using the bayesian method for calculating rates. The color scale representing the lower and upper bounds of the confidence interval.<br />
<br />
- MSA DATA: The number of aligned sequences having an amino acid (non-gapped) from the overall number of sequences at each position.<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ 3LATOM SCORE COLOR CONFIDENCE INTERVAL CONFIDENCE INTERVAL COLORS MSA DATA RESIDUE VARIETY<br />
(normalized) <br />
1 D ASP33: -1.189 9 -1.455,-0.986 9,8 10/29 D <br />
2 V VAL34: 0.979 2* 0.016, 2.633 5,1 10/29 F,N,V,Y <br />
3 N ASN35: -0.318 6 -0.859, 0.016 8,5 14/29 A,N,S,T <br />
4 E GLU36: 0.737 3* 0.016, 1.214 5,1 19/29 E,G,K,Q,S,T <br />
5 M MET37: 0.793 3* 0.016, 1.214 5,1 19/29 A,E,I,L,M,Q,T <br />
6 L LEU38: -1.329 9 -1.588,-1.223 9,9 28/29 L <br />
7 Q GLN39: -0.531 7 -0.859,-0.210 8,6 28/29 K,Q,R <br />
8 S SER40: 2.423 1 2.633, 2.633 1,1 28/29 D,E,K,N,Q,R,S,T <br />
9 A ALA41: 0.058 5 -0.403, 0.294 6,4 28/29 A,G,I,M,N,S,T,V <br />
10 G GLY42: -1.069 8 -1.338,-0.859 9,8 28/29 D,G <br />
11 L LEU43: -0.850 8 -1.223,-0.570 9,7 28/29 I,L,V <br />
12 R ARG44: -0.998 8 -1.223,-0.859 9,8 28/29 K,R <br />
13 P PRO45: 0.305 4 -0.210, 0.661 6,3 28/29 A,I,P,V,Y <br />
14 T THR46: -1.473 9 -1.588,-1.455 9,9 28/29 T <br />
15 R ARG47: 0.816 3* 0.016, 1.214 5,1 28/29 E,F,G,K,L,P,R,V <br />
16 Q GLN48: -0.961 8 -1.223,-0.721 9,7 28/29 P,Q <br />
17 R ARG49: -1.426 9 -1.588,-1.338 9,9 28/29 R <br />
18 M MET50: 0.754 3* 0.016, 1.214 5,1 28/29 E,H,I,L,M,Q,V <br />
19 A ALA51: -0.901 8 -1.223,-0.721 9,7 28/29 A,K,T,V <br />
20 L LEU52: -0.710 7 -0.986,-0.403 8,6 28/29 I,L,V <br />
21 G GLY53: -0.370 6 -0.859, 0.016 8,5 28/29 G,I,L,M <br />
22 W TRP54: 1.698 1 1.214, 2.633 1,1 28/29 A,D,E,K,N,Q,R,W <br />
23 L LEU55: 1.226 1 0.661, 2.633 3,1 28/29 A,F,I,L,M,T,V,Y <br />
24 L LEU56: -0.594 7 -0.986,-0.210 8,6 28/29 F,L,M,V <br />
25 F PHE57: 1.556 1 0.661, 2.633 3,1 28/29 D,E,F,I,K,N,Q,R,V,Y<br />
26 G GLY58: 2.434 1 2.633, 2.633 1,1 28/29 A,E,G,H,K,N,Q,S,T <br />
27 K LYS59: 0.609 3* 0.016, 1.214 5,1 28/29 A,E,H,K,P,S,T <br />
28 G GLY60: 2.294 1 2.633, 2.633 1,1 29/29 A,D,E,G,H,K,M,P,R <br />
29 A ALA61: 2.262 1 2.633, 2.633 1,1 27/29 A,C,E,G,L,M,N,Q,S,T<br />
30 R ARG62: 1.468 1 0.661, 2.633 3,1 19/29 E,H,Q,R <br />
31 H HIS63: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
32 L LEU64: 0.771 3* 0.016, 1.214 5,1 29/29 A,F,I,L,M,P,V,Y <br />
33 T THR65: -0.874 8 -1.107,-0.721 8,7 29/29 D,E,S,T <br />
34 A ALA66: -1.188 9 -1.338,-0.986 9,8 29/29 A,P,T <br />
35 E GLU67: -1.035 8 -1.338,-0.859 9,8 29/29 D,E <br />
36 M MET68: 0.707 3* 0.016, 1.214 5,1 29/29 A,D,E,H,M,S,T <br />
37 L LEU69: 0.078 5 -0.403, 0.294 6,4 29/29 C,I,L,V <br />
38 Y TYR70: -0.574 7 -0.986,-0.210 8,6 29/29 F,I,Y <br />
39 E GLU71: 0.157 5 -0.403, 0.661 6,3 29/29 E,G,K,M,N,Q,R <br />
40 E GLU72: 1.498 1 0.661, 2.633 3,1 29/29 A,E,H,I,K,L,R <br />
41 A ALA73: -0.319 6 -0.721, 0.016 7,5 29/29 A,F,I,L,V <br />
42 T THR74: 1.036 2 0.294, 1.214 4,1 29/29 A,E,I,L,M,R,S,T <br />
43 L LEU75: 1.694 1 0.661, 2.633 3,1 29/29 A,D,E,F,G,L,N,P,S,V<br />
44 A ALA76: 2.302 1 2.633, 2.633 1,1 29/29 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K LYS77: 2.001 1 1.214, 2.633 1,1 29/29 D,F,G,H,K,L,N,S <br />
46 V VAL78: 0.670 3* 0.016, 1.214 5,1 29/29 C,E,L,M,P,S,V <br />
47 P PRO79: 0.328 4 -0.210, 0.661 6,3 29/29 D,E,N,P <br />
48 V VAL80: -0.744 7 -0.986,-0.570 8,7 29/29 I,M,V <br />
49 S SER81: -1.279 9 -1.455,-1.107 9,8 29/29 G,S <br />
50 L LEU82: -0.133 5 -0.570, 0.294 7,4 29/29 H,I,L,R,V <br />
51 A ALA83: -1.171 9 -1.338,-0.986 9,8 29/29 A,Q,S <br />
52 T THR84: -1.376 9 -1.588,-1.223 9,9 29/29 A,T <br />
53 V VAL85: -1.007 8 -1.223,-0.859 9,8 29/29 I,V <br />
54 Y TYR86: -1.335 9 -1.588,-1.223 9,9 29/29 Y <br />
55 N ASN87: -1.123 8 -1.338,-0.986 9,8 29/29 D,N,R <br />
56 T THR88: -0.956 8 -1.223,-0.721 9,7 29/29 N,T,V,X <br />
57 L LEU89: -1.357 9 -1.588,-1.223 9,9 29/29 L <br />
58 N ASN90: -0.647 7 -0.986,-0.403 8,6 29/29 H,K,N,R,T <br />
59 Q GLN91: -0.558 7 -0.859,-0.210 8,6 29/29 A,L,Q,V <br />
60 L LEU92: -0.570 7 -0.986,-0.210 8,6 29/29 F,L,M <br />
61 T THR93: -0.099 5 -0.570, 0.294 7,4 29/29 A,D,E,K,R,T <br />
62 D ASP94: 0.354 4 -0.210, 0.661 6,3 29/29 A,D,E,Q,R,S <br />
63 A ALA95: -0.757 7 -1.107,-0.570 8,7 29/29 A,I,M,S,V <br />
64 G GLY96: -0.841 8 -1.223,-0.570 9,7 29/29 E,G,H <br />
65 L LEU97: -0.306 6 -0.721, 0.016 7,5 29/29 I,L,M <br />
66 L LEU98: -0.712 7 -0.986,-0.403 8,6 29/29 L,V <br />
67 R ARG99: 0.384 4 -0.210, 0.661 6,3 29/29 I,K,L,Q,R,S,T,V <br />
68 Q GLN100: -0.238 6 -0.570, 0.016 7,5 29/29 E,K,Q,R,S <br />
69 V VAL101: -0.147 5 -0.570, 0.294 7,4 29/29 H,I,L,N,S,V <br />
70 S SER102: 0.078 5 -0.403, 0.294 6,4 29/29 D,H,N,P,Q,S,T <br />
71 V VAL103: 0.145 5 -0.403, 0.661 6,3 29/29 F,L,P,V,Y <br />
72 D ASP104: 0.881 2 0.294, 1.214 4,1 29/29 A,D,E,G,S,T <br />
73 G GLY105: 0.110 5 -0.403, 0.661 6,3 29/29 D,E,G,S,T <br />
74 T THR106: -0.006 5 -0.403, 0.294 6,4 29/29 A,D,G,N,S,T <br />
75 K LYS107: 0.077 5 -0.403, 0.294 6,4 29/29 G,H,K,S,V <br />
76 T THR108: -0.179 6 -0.570, 0.016 7,5 29/29 A,K,S,T <br />
77 Y TYR109: -0.415 6 -0.721,-0.210 7,6 29/29 H,I,K,R,V,Y <br />
78 F PHE110: -0.368 6 -0.721, 0.016 7,5 29/29 F,Y <br />
79 D ASP111: -1.082 8 -1.338,-0.859 9,8 29/29 D,E <br />
80 T THR112: -0.448 6 -0.859,-0.210 8,6 29/29 F,L,S,T <br />
81 N ASN113: 0.772 3 0.294, 1.214 4,1 29/29 A,D,N,R,S,T,V <br />
82 V VAL114: 0.383 4* -0.570, 1.214 7,1 2/29 Q,V <br />
83 T THR115: 2.165 1 1.214, 2.633 1,1 23/29 D,E,K,N,P,Q,T,V <br />
84 T THR116: 1.506 1 0.661, 2.633 3,1 29/29 D,G,K,L,N,Q,S,T <br />
85 H HIS117: 1.472 1 0.661, 2.633 3,1 29/29 D,E,G,H,K,P,S <br />
86 H HIS118: -0.825 8 -1.107,-0.570 8,7 29/29 D,E,H,N <br />
87 H HIS119: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
88 Y TYR120: -0.874 8 -1.107,-0.721 8,7 29/29 D,H,Y <br />
89 Y TYR121: -1.329 9 -1.455,-1.223 9,9 29/29 H,Y <br />
90 L LEU122: 1.136 2 0.294, 1.214 4,1 25/29 A,I,L,M,V <br />
91 E GLU123: 1.417 1 0.661, 2.633 3,1 18/29 E,K,L,M,T,V <br />
92 N ASN124: 0.930 2* 0.016, 1.214 5,1 18/29 D,E,K,N,Q,V <br />
93 S SER125: -0.572 7 -0.986,-0.210 8,6 18/29 C,S,T <br />
94 H HIS126: -0.108 5 -0.721, 0.294 7,4 18/29 G,H,N,S <br />
95 E GLU127: -0.355 6 -0.859, 0.016 8,5 18/29 E,K,T <br />
96 L LEU128: -0.913 8 -1.223,-0.721 9,7 18/29 I,L,V <br />
97 V VAL129: -0.280 6 -0.721, 0.016 7,5 18/29 F,I,T,V <br />
98 D ASP130: -1.063 8 -1.338,-0.859 9,8 18/29 D,E <br />
99 I ILE131: -0.905 8 -1.223,-0.721 9,7 18/29 F,I <br />
100 E GLU132: 1.739 1 1.214, 2.633 1,1 18/29 E,H,K,M,Q,S,T <br />
101 D ASP133: -0.254 6 -0.721, 0.016 7,5 18/29 D,N,S,Y <br />
102 P PRO134: -0.193 6 -0.721, 0.294 7,4 18/29 A,E,N,P <br />
103 H HIS135: 1.561 1 0.661, 2.633 3,1 16/29 D,E,G,H,I,Q,V <br />
104 L LEU136: -1.023 8 -1.338,-0.859 9,8 16/29 I,L <br />
105 A ALA137: 0.666 3* -0.210, 1.214 6,1 7/29 A,K,Q <br />
106 L LEU138: 0.051 5* -0.721, 0.661 7,3 7/29 L,R <br />
107 S SER139: -0.624 7 -1.107,-0.210 8,6 7/29 Q,S <br />
108 K LYS140: 0.661 3* -0.210, 1.214 6,1 7/29 D,K,R <br />
109 M MET141: 0.164 4* -0.570, 0.661 7,3 7/29 E,K,M <br />
110 P PRO142: -0.492 7 -0.986,-0.210 8,6 7/29 I,P <br />
111 E GLU143: 0.243 4* -0.570, 0.661 7,3 7/29 A,E,S,V <br />
112 V VAL144: 0.835 2* 0.016, 1.214 5,1 7/29 A,E,R,V <br />
113 P PRO145: 0.779 3* 0.016, 1.214 5,1 7/29 E,K,P,Q <br />
114 E GLU146: 1.555 1 0.661, 2.633 3,1 7/29 E,H,N,R,Y <br />
115 G GLY147: -0.540 7 -1.107,-0.210 8,6 7/29 G,N <br />
116 Y TYR148: 1.072 2 0.294, 2.633 4,1 7/29 F,I,V,Y <br />
117 E GLU149: -0.017 5* -0.859, 0.661 8,3 5/29 E,R <br />
118 I ILE150: -0.332 6* -0.986, 0.016 8,5 5/29 I,L <br />
119 A ALA151: -0.318 6* -0.986, 0.016 8,5 3/29 A,V <br />
120 R ARG152: 0.307 4* -0.570, 1.214 7,1 3/29 D,R <br />
121 I ILE153: 0.330 4* -0.570, 1.214 7,1 3/29 H,I <br />
122 D ASP154: -0.429 6* -1.107, 0.016 8,5 3/29 D,N <br />
123 M MET155: -0.296 6* -0.986, 0.016 8,5 3/29 L,M <br />
124 V VAL156: -0.946 8* -1.455,-0.721 9,7 3/29 V <br />
125 V VAL157: -0.137 5* -0.859, 0.294 8,4 3/29 L,V <br />
126 R ARG158: 0.277 4* -0.570, 1.214 7,1 3/29 R,Y <br />
127 L LEU159: -0.174 6* -0.859, 0.294 8,4 3/29 L,V <br />
128 R ARG160: -0.959 8* -1.455,-0.721 9,7 3/29 R <br />
129 K LYS161: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
130 K LYS162: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
131 R ARG163: -0.419 6* -1.107, 0.016 8,5 3/29 K,R <br />
<br />
<br />
<br />
=Structure of the Proposed Irr Protein=<br />
<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951420User:Adam Meade/Sandbox 12009-04-27T15:26:08Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
----<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
----<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Function of Irr'''<br />
----<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Chemical and Physical Properties of Irr'''<br />
----<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
'''Evolution of Irr/Fur'''<br />
----<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- 3LATOM: The ATOM derived sequence in three letter code, including the AA's positions as they appear in the PDB file and the chain identifier.<br />
<br />
- SCORE: The normalized conservation scores.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- CONFIDENCE INTERVAL: When using the bayesian method for calculating rates, a confidence interval is assigned to each of the inferred evolutionary conservation scores.<br />
<br />
- CONFIDENCE INTERVAL COLORS: When using the bayesian method for calculating rates. The color scale representing the lower and upper bounds of the confidence interval.<br />
<br />
- MSA DATA: The number of aligned sequences having an amino acid (non-gapped) from the overall number of sequences at each position.<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
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<br />
<br />
POS SEQ 3LATOM SCORE COLOR CONFIDENCE INTERVAL CONFIDENCE INTERVAL COLORS MSA DATA RESIDUE VARIETY<br />
(normalized) <br />
1 D ASP33: -1.189 9 -1.455,-0.986 9,8 10/29 D <br />
2 V VAL34: 0.979 2* 0.016, 2.633 5,1 10/29 F,N,V,Y <br />
3 N ASN35: -0.318 6 -0.859, 0.016 8,5 14/29 A,N,S,T <br />
4 E GLU36: 0.737 3* 0.016, 1.214 5,1 19/29 E,G,K,Q,S,T <br />
5 M MET37: 0.793 3* 0.016, 1.214 5,1 19/29 A,E,I,L,M,Q,T <br />
6 L LEU38: -1.329 9 -1.588,-1.223 9,9 28/29 L <br />
7 Q GLN39: -0.531 7 -0.859,-0.210 8,6 28/29 K,Q,R <br />
8 S SER40: 2.423 1 2.633, 2.633 1,1 28/29 D,E,K,N,Q,R,S,T <br />
9 A ALA41: 0.058 5 -0.403, 0.294 6,4 28/29 A,G,I,M,N,S,T,V <br />
10 G GLY42: -1.069 8 -1.338,-0.859 9,8 28/29 D,G <br />
11 L LEU43: -0.850 8 -1.223,-0.570 9,7 28/29 I,L,V <br />
12 R ARG44: -0.998 8 -1.223,-0.859 9,8 28/29 K,R <br />
13 P PRO45: 0.305 4 -0.210, 0.661 6,3 28/29 A,I,P,V,Y <br />
14 T THR46: -1.473 9 -1.588,-1.455 9,9 28/29 T <br />
15 R ARG47: 0.816 3* 0.016, 1.214 5,1 28/29 E,F,G,K,L,P,R,V <br />
16 Q GLN48: -0.961 8 -1.223,-0.721 9,7 28/29 P,Q <br />
17 R ARG49: -1.426 9 -1.588,-1.338 9,9 28/29 R <br />
18 M MET50: 0.754 3* 0.016, 1.214 5,1 28/29 E,H,I,L,M,Q,V <br />
19 A ALA51: -0.901 8 -1.223,-0.721 9,7 28/29 A,K,T,V <br />
20 L LEU52: -0.710 7 -0.986,-0.403 8,6 28/29 I,L,V <br />
21 G GLY53: -0.370 6 -0.859, 0.016 8,5 28/29 G,I,L,M <br />
22 W TRP54: 1.698 1 1.214, 2.633 1,1 28/29 A,D,E,K,N,Q,R,W <br />
23 L LEU55: 1.226 1 0.661, 2.633 3,1 28/29 A,F,I,L,M,T,V,Y <br />
24 L LEU56: -0.594 7 -0.986,-0.210 8,6 28/29 F,L,M,V <br />
25 F PHE57: 1.556 1 0.661, 2.633 3,1 28/29 D,E,F,I,K,N,Q,R,V,Y<br />
26 G GLY58: 2.434 1 2.633, 2.633 1,1 28/29 A,E,G,H,K,N,Q,S,T <br />
27 K LYS59: 0.609 3* 0.016, 1.214 5,1 28/29 A,E,H,K,P,S,T <br />
28 G GLY60: 2.294 1 2.633, 2.633 1,1 29/29 A,D,E,G,H,K,M,P,R <br />
29 A ALA61: 2.262 1 2.633, 2.633 1,1 27/29 A,C,E,G,L,M,N,Q,S,T<br />
30 R ARG62: 1.468 1 0.661, 2.633 3,1 19/29 E,H,Q,R <br />
31 H HIS63: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
32 L LEU64: 0.771 3* 0.016, 1.214 5,1 29/29 A,F,I,L,M,P,V,Y <br />
33 T THR65: -0.874 8 -1.107,-0.721 8,7 29/29 D,E,S,T <br />
34 A ALA66: -1.188 9 -1.338,-0.986 9,8 29/29 A,P,T <br />
35 E GLU67: -1.035 8 -1.338,-0.859 9,8 29/29 D,E <br />
36 M MET68: 0.707 3* 0.016, 1.214 5,1 29/29 A,D,E,H,M,S,T <br />
37 L LEU69: 0.078 5 -0.403, 0.294 6,4 29/29 C,I,L,V <br />
38 Y TYR70: -0.574 7 -0.986,-0.210 8,6 29/29 F,I,Y <br />
39 E GLU71: 0.157 5 -0.403, 0.661 6,3 29/29 E,G,K,M,N,Q,R <br />
40 E GLU72: 1.498 1 0.661, 2.633 3,1 29/29 A,E,H,I,K,L,R <br />
41 A ALA73: -0.319 6 -0.721, 0.016 7,5 29/29 A,F,I,L,V <br />
42 T THR74: 1.036 2 0.294, 1.214 4,1 29/29 A,E,I,L,M,R,S,T <br />
43 L LEU75: 1.694 1 0.661, 2.633 3,1 29/29 A,D,E,F,G,L,N,P,S,V<br />
44 A ALA76: 2.302 1 2.633, 2.633 1,1 29/29 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K LYS77: 2.001 1 1.214, 2.633 1,1 29/29 D,F,G,H,K,L,N,S <br />
46 V VAL78: 0.670 3* 0.016, 1.214 5,1 29/29 C,E,L,M,P,S,V <br />
47 P PRO79: 0.328 4 -0.210, 0.661 6,3 29/29 D,E,N,P <br />
48 V VAL80: -0.744 7 -0.986,-0.570 8,7 29/29 I,M,V <br />
49 S SER81: -1.279 9 -1.455,-1.107 9,8 29/29 G,S <br />
50 L LEU82: -0.133 5 -0.570, 0.294 7,4 29/29 H,I,L,R,V <br />
51 A ALA83: -1.171 9 -1.338,-0.986 9,8 29/29 A,Q,S <br />
52 T THR84: -1.376 9 -1.588,-1.223 9,9 29/29 A,T <br />
53 V VAL85: -1.007 8 -1.223,-0.859 9,8 29/29 I,V <br />
54 Y TYR86: -1.335 9 -1.588,-1.223 9,9 29/29 Y <br />
55 N ASN87: -1.123 8 -1.338,-0.986 9,8 29/29 D,N,R <br />
56 T THR88: -0.956 8 -1.223,-0.721 9,7 29/29 N,T,V,X <br />
57 L LEU89: -1.357 9 -1.588,-1.223 9,9 29/29 L <br />
58 N ASN90: -0.647 7 -0.986,-0.403 8,6 29/29 H,K,N,R,T <br />
59 Q GLN91: -0.558 7 -0.859,-0.210 8,6 29/29 A,L,Q,V <br />
60 L LEU92: -0.570 7 -0.986,-0.210 8,6 29/29 F,L,M <br />
61 T THR93: -0.099 5 -0.570, 0.294 7,4 29/29 A,D,E,K,R,T <br />
62 D ASP94: 0.354 4 -0.210, 0.661 6,3 29/29 A,D,E,Q,R,S <br />
63 A ALA95: -0.757 7 -1.107,-0.570 8,7 29/29 A,I,M,S,V <br />
64 G GLY96: -0.841 8 -1.223,-0.570 9,7 29/29 E,G,H <br />
65 L LEU97: -0.306 6 -0.721, 0.016 7,5 29/29 I,L,M <br />
66 L LEU98: -0.712 7 -0.986,-0.403 8,6 29/29 L,V <br />
67 R ARG99: 0.384 4 -0.210, 0.661 6,3 29/29 I,K,L,Q,R,S,T,V <br />
68 Q GLN100: -0.238 6 -0.570, 0.016 7,5 29/29 E,K,Q,R,S <br />
69 V VAL101: -0.147 5 -0.570, 0.294 7,4 29/29 H,I,L,N,S,V <br />
70 S SER102: 0.078 5 -0.403, 0.294 6,4 29/29 D,H,N,P,Q,S,T <br />
71 V VAL103: 0.145 5 -0.403, 0.661 6,3 29/29 F,L,P,V,Y <br />
72 D ASP104: 0.881 2 0.294, 1.214 4,1 29/29 A,D,E,G,S,T <br />
73 G GLY105: 0.110 5 -0.403, 0.661 6,3 29/29 D,E,G,S,T <br />
74 T THR106: -0.006 5 -0.403, 0.294 6,4 29/29 A,D,G,N,S,T <br />
75 K LYS107: 0.077 5 -0.403, 0.294 6,4 29/29 G,H,K,S,V <br />
76 T THR108: -0.179 6 -0.570, 0.016 7,5 29/29 A,K,S,T <br />
77 Y TYR109: -0.415 6 -0.721,-0.210 7,6 29/29 H,I,K,R,V,Y <br />
78 F PHE110: -0.368 6 -0.721, 0.016 7,5 29/29 F,Y <br />
79 D ASP111: -1.082 8 -1.338,-0.859 9,8 29/29 D,E <br />
80 T THR112: -0.448 6 -0.859,-0.210 8,6 29/29 F,L,S,T <br />
81 N ASN113: 0.772 3 0.294, 1.214 4,1 29/29 A,D,N,R,S,T,V <br />
82 V VAL114: 0.383 4* -0.570, 1.214 7,1 2/29 Q,V <br />
83 T THR115: 2.165 1 1.214, 2.633 1,1 23/29 D,E,K,N,P,Q,T,V <br />
84 T THR116: 1.506 1 0.661, 2.633 3,1 29/29 D,G,K,L,N,Q,S,T <br />
85 H HIS117: 1.472 1 0.661, 2.633 3,1 29/29 D,E,G,H,K,P,S <br />
86 H HIS118: -0.825 8 -1.107,-0.570 8,7 29/29 D,E,H,N <br />
87 H HIS119: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
88 Y TYR120: -0.874 8 -1.107,-0.721 8,7 29/29 D,H,Y <br />
89 Y TYR121: -1.329 9 -1.455,-1.223 9,9 29/29 H,Y <br />
90 L LEU122: 1.136 2 0.294, 1.214 4,1 25/29 A,I,L,M,V <br />
91 E GLU123: 1.417 1 0.661, 2.633 3,1 18/29 E,K,L,M,T,V <br />
92 N ASN124: 0.930 2* 0.016, 1.214 5,1 18/29 D,E,K,N,Q,V <br />
93 S SER125: -0.572 7 -0.986,-0.210 8,6 18/29 C,S,T <br />
94 H HIS126: -0.108 5 -0.721, 0.294 7,4 18/29 G,H,N,S <br />
95 E GLU127: -0.355 6 -0.859, 0.016 8,5 18/29 E,K,T <br />
96 L LEU128: -0.913 8 -1.223,-0.721 9,7 18/29 I,L,V <br />
97 V VAL129: -0.280 6 -0.721, 0.016 7,5 18/29 F,I,T,V <br />
98 D ASP130: -1.063 8 -1.338,-0.859 9,8 18/29 D,E <br />
99 I ILE131: -0.905 8 -1.223,-0.721 9,7 18/29 F,I <br />
100 E GLU132: 1.739 1 1.214, 2.633 1,1 18/29 E,H,K,M,Q,S,T <br />
101 D ASP133: -0.254 6 -0.721, 0.016 7,5 18/29 D,N,S,Y <br />
102 P PRO134: -0.193 6 -0.721, 0.294 7,4 18/29 A,E,N,P <br />
103 H HIS135: 1.561 1 0.661, 2.633 3,1 16/29 D,E,G,H,I,Q,V <br />
104 L LEU136: -1.023 8 -1.338,-0.859 9,8 16/29 I,L <br />
105 A ALA137: 0.666 3* -0.210, 1.214 6,1 7/29 A,K,Q <br />
106 L LEU138: 0.051 5* -0.721, 0.661 7,3 7/29 L,R <br />
107 S SER139: -0.624 7 -1.107,-0.210 8,6 7/29 Q,S <br />
108 K LYS140: 0.661 3* -0.210, 1.214 6,1 7/29 D,K,R <br />
109 M MET141: 0.164 4* -0.570, 0.661 7,3 7/29 E,K,M <br />
110 P PRO142: -0.492 7 -0.986,-0.210 8,6 7/29 I,P <br />
111 E GLU143: 0.243 4* -0.570, 0.661 7,3 7/29 A,E,S,V <br />
112 V VAL144: 0.835 2* 0.016, 1.214 5,1 7/29 A,E,R,V <br />
113 P PRO145: 0.779 3* 0.016, 1.214 5,1 7/29 E,K,P,Q <br />
114 E GLU146: 1.555 1 0.661, 2.633 3,1 7/29 E,H,N,R,Y <br />
115 G GLY147: -0.540 7 -1.107,-0.210 8,6 7/29 G,N <br />
116 Y TYR148: 1.072 2 0.294, 2.633 4,1 7/29 F,I,V,Y <br />
117 E GLU149: -0.017 5* -0.859, 0.661 8,3 5/29 E,R <br />
118 I ILE150: -0.332 6* -0.986, 0.016 8,5 5/29 I,L <br />
119 A ALA151: -0.318 6* -0.986, 0.016 8,5 3/29 A,V <br />
120 R ARG152: 0.307 4* -0.570, 1.214 7,1 3/29 D,R <br />
121 I ILE153: 0.330 4* -0.570, 1.214 7,1 3/29 H,I <br />
122 D ASP154: -0.429 6* -1.107, 0.016 8,5 3/29 D,N <br />
123 M MET155: -0.296 6* -0.986, 0.016 8,5 3/29 L,M <br />
124 V VAL156: -0.946 8* -1.455,-0.721 9,7 3/29 V <br />
125 V VAL157: -0.137 5* -0.859, 0.294 8,4 3/29 L,V <br />
126 R ARG158: 0.277 4* -0.570, 1.214 7,1 3/29 R,Y <br />
127 L LEU159: -0.174 6* -0.859, 0.294 8,4 3/29 L,V <br />
128 R ARG160: -0.959 8* -1.455,-0.721 9,7 3/29 R <br />
129 K LYS161: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
130 K LYS162: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
131 R ARG163: -0.419 6* -1.107, 0.016 8,5 3/29 K,R <br />
<br />
<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
----<br />
<br />
<scene name='User:Adam_Meade/Sandbox_1/Secondary_structure_-_irr/1'>Secondary Structure</scene><br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951408User:Adam Meade/Sandbox 12009-04-27T15:05:09Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
----<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
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'''Irr and Other Iron-Regulating Proteins'''<br />
----<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
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'''Function of Irr'''<br />
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Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
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Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
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'''Chemical and Physical Properties of Irr'''<br />
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Molecular weight: 18338.8 Da<br />
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Theoretical pI: 6.03<br />
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{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
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'''Evolution of Irr/Fur'''<br />
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Amino Acid Conservation Scores<br />
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The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
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- POS: The position of the AA in the SEQRES derived sequence.<br />
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- SEQ: The SEQRES derived sequence in one letter code.<br />
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- 3LATOM: The ATOM derived sequence in three letter code, including the AA's positions as they appear in the PDB file and the chain identifier.<br />
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- SCORE: The normalized conservation scores.<br />
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- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
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- CONFIDENCE INTERVAL: When using the bayesian method for calculating rates, a confidence interval is assigned to each of the inferred evolutionary conservation scores.<br />
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- CONFIDENCE INTERVAL COLORS: When using the bayesian method for calculating rates. The color scale representing the lower and upper bounds of the confidence interval.<br />
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- MSA DATA: The number of aligned sequences having an amino acid (non-gapped) from the overall number of sequences at each position.<br />
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- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
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POS SEQ 3LATOM SCORE COLOR CONFIDENCE INTERVAL CONFIDENCE INTERVAL COLORS MSA DATA RESIDUE VARIETY<br />
(normalized) <br />
1 D ASP33: -1.189 9 -1.455,-0.986 9,8 10/29 D <br />
2 V VAL34: 0.979 2* 0.016, 2.633 5,1 10/29 F,N,V,Y <br />
3 N ASN35: -0.318 6 -0.859, 0.016 8,5 14/29 A,N,S,T <br />
4 E GLU36: 0.737 3* 0.016, 1.214 5,1 19/29 E,G,K,Q,S,T <br />
5 M MET37: 0.793 3* 0.016, 1.214 5,1 19/29 A,E,I,L,M,Q,T <br />
6 L LEU38: -1.329 9 -1.588,-1.223 9,9 28/29 L <br />
7 Q GLN39: -0.531 7 -0.859,-0.210 8,6 28/29 K,Q,R <br />
8 S SER40: 2.423 1 2.633, 2.633 1,1 28/29 D,E,K,N,Q,R,S,T <br />
9 A ALA41: 0.058 5 -0.403, 0.294 6,4 28/29 A,G,I,M,N,S,T,V <br />
10 G GLY42: -1.069 8 -1.338,-0.859 9,8 28/29 D,G <br />
11 L LEU43: -0.850 8 -1.223,-0.570 9,7 28/29 I,L,V <br />
12 R ARG44: -0.998 8 -1.223,-0.859 9,8 28/29 K,R <br />
13 P PRO45: 0.305 4 -0.210, 0.661 6,3 28/29 A,I,P,V,Y <br />
14 T THR46: -1.473 9 -1.588,-1.455 9,9 28/29 T <br />
15 R ARG47: 0.816 3* 0.016, 1.214 5,1 28/29 E,F,G,K,L,P,R,V <br />
16 Q GLN48: -0.961 8 -1.223,-0.721 9,7 28/29 P,Q <br />
17 R ARG49: -1.426 9 -1.588,-1.338 9,9 28/29 R <br />
18 M MET50: 0.754 3* 0.016, 1.214 5,1 28/29 E,H,I,L,M,Q,V <br />
19 A ALA51: -0.901 8 -1.223,-0.721 9,7 28/29 A,K,T,V <br />
20 L LEU52: -0.710 7 -0.986,-0.403 8,6 28/29 I,L,V <br />
21 G GLY53: -0.370 6 -0.859, 0.016 8,5 28/29 G,I,L,M <br />
22 W TRP54: 1.698 1 1.214, 2.633 1,1 28/29 A,D,E,K,N,Q,R,W <br />
23 L LEU55: 1.226 1 0.661, 2.633 3,1 28/29 A,F,I,L,M,T,V,Y <br />
24 L LEU56: -0.594 7 -0.986,-0.210 8,6 28/29 F,L,M,V <br />
25 F PHE57: 1.556 1 0.661, 2.633 3,1 28/29 D,E,F,I,K,N,Q,R,V,Y<br />
26 G GLY58: 2.434 1 2.633, 2.633 1,1 28/29 A,E,G,H,K,N,Q,S,T <br />
27 K LYS59: 0.609 3* 0.016, 1.214 5,1 28/29 A,E,H,K,P,S,T <br />
28 G GLY60: 2.294 1 2.633, 2.633 1,1 29/29 A,D,E,G,H,K,M,P,R <br />
29 A ALA61: 2.262 1 2.633, 2.633 1,1 27/29 A,C,E,G,L,M,N,Q,S,T<br />
30 R ARG62: 1.468 1 0.661, 2.633 3,1 19/29 E,H,Q,R <br />
31 H HIS63: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
32 L LEU64: 0.771 3* 0.016, 1.214 5,1 29/29 A,F,I,L,M,P,V,Y <br />
33 T THR65: -0.874 8 -1.107,-0.721 8,7 29/29 D,E,S,T <br />
34 A ALA66: -1.188 9 -1.338,-0.986 9,8 29/29 A,P,T <br />
35 E GLU67: -1.035 8 -1.338,-0.859 9,8 29/29 D,E <br />
36 M MET68: 0.707 3* 0.016, 1.214 5,1 29/29 A,D,E,H,M,S,T <br />
37 L LEU69: 0.078 5 -0.403, 0.294 6,4 29/29 C,I,L,V <br />
38 Y TYR70: -0.574 7 -0.986,-0.210 8,6 29/29 F,I,Y <br />
39 E GLU71: 0.157 5 -0.403, 0.661 6,3 29/29 E,G,K,M,N,Q,R <br />
40 E GLU72: 1.498 1 0.661, 2.633 3,1 29/29 A,E,H,I,K,L,R <br />
41 A ALA73: -0.319 6 -0.721, 0.016 7,5 29/29 A,F,I,L,V <br />
42 T THR74: 1.036 2 0.294, 1.214 4,1 29/29 A,E,I,L,M,R,S,T <br />
43 L LEU75: 1.694 1 0.661, 2.633 3,1 29/29 A,D,E,F,G,L,N,P,S,V<br />
44 A ALA76: 2.302 1 2.633, 2.633 1,1 29/29 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K LYS77: 2.001 1 1.214, 2.633 1,1 29/29 D,F,G,H,K,L,N,S <br />
46 V VAL78: 0.670 3* 0.016, 1.214 5,1 29/29 C,E,L,M,P,S,V <br />
47 P PRO79: 0.328 4 -0.210, 0.661 6,3 29/29 D,E,N,P <br />
48 V VAL80: -0.744 7 -0.986,-0.570 8,7 29/29 I,M,V <br />
49 S SER81: -1.279 9 -1.455,-1.107 9,8 29/29 G,S <br />
50 L LEU82: -0.133 5 -0.570, 0.294 7,4 29/29 H,I,L,R,V <br />
51 A ALA83: -1.171 9 -1.338,-0.986 9,8 29/29 A,Q,S <br />
52 T THR84: -1.376 9 -1.588,-1.223 9,9 29/29 A,T <br />
53 V VAL85: -1.007 8 -1.223,-0.859 9,8 29/29 I,V <br />
54 Y TYR86: -1.335 9 -1.588,-1.223 9,9 29/29 Y <br />
55 N ASN87: -1.123 8 -1.338,-0.986 9,8 29/29 D,N,R <br />
56 T THR88: -0.956 8 -1.223,-0.721 9,7 29/29 N,T,V,X <br />
57 L LEU89: -1.357 9 -1.588,-1.223 9,9 29/29 L <br />
58 N ASN90: -0.647 7 -0.986,-0.403 8,6 29/29 H,K,N,R,T <br />
59 Q GLN91: -0.558 7 -0.859,-0.210 8,6 29/29 A,L,Q,V <br />
60 L LEU92: -0.570 7 -0.986,-0.210 8,6 29/29 F,L,M <br />
61 T THR93: -0.099 5 -0.570, 0.294 7,4 29/29 A,D,E,K,R,T <br />
62 D ASP94: 0.354 4 -0.210, 0.661 6,3 29/29 A,D,E,Q,R,S <br />
63 A ALA95: -0.757 7 -1.107,-0.570 8,7 29/29 A,I,M,S,V <br />
64 G GLY96: -0.841 8 -1.223,-0.570 9,7 29/29 E,G,H <br />
65 L LEU97: -0.306 6 -0.721, 0.016 7,5 29/29 I,L,M <br />
66 L LEU98: -0.712 7 -0.986,-0.403 8,6 29/29 L,V <br />
67 R ARG99: 0.384 4 -0.210, 0.661 6,3 29/29 I,K,L,Q,R,S,T,V <br />
68 Q GLN100: -0.238 6 -0.570, 0.016 7,5 29/29 E,K,Q,R,S <br />
69 V VAL101: -0.147 5 -0.570, 0.294 7,4 29/29 H,I,L,N,S,V <br />
70 S SER102: 0.078 5 -0.403, 0.294 6,4 29/29 D,H,N,P,Q,S,T <br />
71 V VAL103: 0.145 5 -0.403, 0.661 6,3 29/29 F,L,P,V,Y <br />
72 D ASP104: 0.881 2 0.294, 1.214 4,1 29/29 A,D,E,G,S,T <br />
73 G GLY105: 0.110 5 -0.403, 0.661 6,3 29/29 D,E,G,S,T <br />
74 T THR106: -0.006 5 -0.403, 0.294 6,4 29/29 A,D,G,N,S,T <br />
75 K LYS107: 0.077 5 -0.403, 0.294 6,4 29/29 G,H,K,S,V <br />
76 T THR108: -0.179 6 -0.570, 0.016 7,5 29/29 A,K,S,T <br />
77 Y TYR109: -0.415 6 -0.721,-0.210 7,6 29/29 H,I,K,R,V,Y <br />
78 F PHE110: -0.368 6 -0.721, 0.016 7,5 29/29 F,Y <br />
79 D ASP111: -1.082 8 -1.338,-0.859 9,8 29/29 D,E <br />
80 T THR112: -0.448 6 -0.859,-0.210 8,6 29/29 F,L,S,T <br />
81 N ASN113: 0.772 3 0.294, 1.214 4,1 29/29 A,D,N,R,S,T,V <br />
82 V VAL114: 0.383 4* -0.570, 1.214 7,1 2/29 Q,V <br />
83 T THR115: 2.165 1 1.214, 2.633 1,1 23/29 D,E,K,N,P,Q,T,V <br />
84 T THR116: 1.506 1 0.661, 2.633 3,1 29/29 D,G,K,L,N,Q,S,T <br />
85 H HIS117: 1.472 1 0.661, 2.633 3,1 29/29 D,E,G,H,K,P,S <br />
86 H HIS118: -0.825 8 -1.107,-0.570 8,7 29/29 D,E,H,N <br />
87 H HIS119: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
88 Y TYR120: -0.874 8 -1.107,-0.721 8,7 29/29 D,H,Y <br />
89 Y TYR121: -1.329 9 -1.455,-1.223 9,9 29/29 H,Y <br />
90 L LEU122: 1.136 2 0.294, 1.214 4,1 25/29 A,I,L,M,V <br />
91 E GLU123: 1.417 1 0.661, 2.633 3,1 18/29 E,K,L,M,T,V <br />
92 N ASN124: 0.930 2* 0.016, 1.214 5,1 18/29 D,E,K,N,Q,V <br />
93 S SER125: -0.572 7 -0.986,-0.210 8,6 18/29 C,S,T <br />
94 H HIS126: -0.108 5 -0.721, 0.294 7,4 18/29 G,H,N,S <br />
95 E GLU127: -0.355 6 -0.859, 0.016 8,5 18/29 E,K,T <br />
96 L LEU128: -0.913 8 -1.223,-0.721 9,7 18/29 I,L,V <br />
97 V VAL129: -0.280 6 -0.721, 0.016 7,5 18/29 F,I,T,V <br />
98 D ASP130: -1.063 8 -1.338,-0.859 9,8 18/29 D,E <br />
99 I ILE131: -0.905 8 -1.223,-0.721 9,7 18/29 F,I <br />
100 E GLU132: 1.739 1 1.214, 2.633 1,1 18/29 E,H,K,M,Q,S,T <br />
101 D ASP133: -0.254 6 -0.721, 0.016 7,5 18/29 D,N,S,Y <br />
102 P PRO134: -0.193 6 -0.721, 0.294 7,4 18/29 A,E,N,P <br />
103 H HIS135: 1.561 1 0.661, 2.633 3,1 16/29 D,E,G,H,I,Q,V <br />
104 L LEU136: -1.023 8 -1.338,-0.859 9,8 16/29 I,L <br />
105 A ALA137: 0.666 3* -0.210, 1.214 6,1 7/29 A,K,Q <br />
106 L LEU138: 0.051 5* -0.721, 0.661 7,3 7/29 L,R <br />
107 S SER139: -0.624 7 -1.107,-0.210 8,6 7/29 Q,S <br />
108 K LYS140: 0.661 3* -0.210, 1.214 6,1 7/29 D,K,R <br />
109 M MET141: 0.164 4* -0.570, 0.661 7,3 7/29 E,K,M <br />
110 P PRO142: -0.492 7 -0.986,-0.210 8,6 7/29 I,P <br />
111 E GLU143: 0.243 4* -0.570, 0.661 7,3 7/29 A,E,S,V <br />
112 V VAL144: 0.835 2* 0.016, 1.214 5,1 7/29 A,E,R,V <br />
113 P PRO145: 0.779 3* 0.016, 1.214 5,1 7/29 E,K,P,Q <br />
114 E GLU146: 1.555 1 0.661, 2.633 3,1 7/29 E,H,N,R,Y <br />
115 G GLY147: -0.540 7 -1.107,-0.210 8,6 7/29 G,N <br />
116 Y TYR148: 1.072 2 0.294, 2.633 4,1 7/29 F,I,V,Y <br />
117 E GLU149: -0.017 5* -0.859, 0.661 8,3 5/29 E,R <br />
118 I ILE150: -0.332 6* -0.986, 0.016 8,5 5/29 I,L <br />
119 A ALA151: -0.318 6* -0.986, 0.016 8,5 3/29 A,V <br />
120 R ARG152: 0.307 4* -0.570, 1.214 7,1 3/29 D,R <br />
121 I ILE153: 0.330 4* -0.570, 1.214 7,1 3/29 H,I <br />
122 D ASP154: -0.429 6* -1.107, 0.016 8,5 3/29 D,N <br />
123 M MET155: -0.296 6* -0.986, 0.016 8,5 3/29 L,M <br />
124 V VAL156: -0.946 8* -1.455,-0.721 9,7 3/29 V <br />
125 V VAL157: -0.137 5* -0.859, 0.294 8,4 3/29 L,V <br />
126 R ARG158: 0.277 4* -0.570, 1.214 7,1 3/29 R,Y <br />
127 L LEU159: -0.174 6* -0.859, 0.294 8,4 3/29 L,V <br />
128 R ARG160: -0.959 8* -1.455,-0.721 9,7 3/29 R <br />
129 K LYS161: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
130 K LYS162: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
131 R ARG163: -0.419 6* -1.107, 0.016 8,5 3/29 K,R <br />
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<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
----<br />
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The amino acid sequence used to derive the structure shown is as follows:<br />
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1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
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61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
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121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
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<br />
[[image:irr.png|400px]]<br />
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==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951403User:Adam Meade/Sandbox 12009-04-27T14:57:16Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
----<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
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<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
----<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Function of Irr'''<br />
----<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
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<br />
<br />
'''Chemical and Physical Properties of Irr'''<br />
----<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
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<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
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<br />
<br />
'''Evolution of Irr/Fur'''<br />
----<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
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- POS: The position of the AA in the SEQRES derived sequence.<br />
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- SEQ: The SEQRES derived sequence in one letter code.<br />
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- 3LATOM: The ATOM derived sequence in three letter code, including the AA's positions as they appear in the PDB file and the chain identifier.<br />
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- SCORE: The normalized conservation scores.<br />
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- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
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- CONFIDENCE INTERVAL: When using the bayesian method for calculating rates, a confidence interval is assigned to each of the inferred evolutionary conservation scores.<br />
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- CONFIDENCE INTERVAL COLORS: When using the bayesian method for calculating rates. The color scale representing the lower and upper bounds of the confidence interval.<br />
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- MSA DATA: The number of aligned sequences having an amino acid (non-gapped) from the overall number of sequences at each position.<br />
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- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
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<br />
POS SEQ 3LATOM SCORE COLOR CONFIDENCE INTERVAL CONFIDENCE INTERVAL COLORS MSA DATA RESIDUE VARIETY<br />
(normalized) <br />
1 D ASP33: -1.189 9 -1.455,-0.986 9,8 10/29 D <br />
2 V VAL34: 0.979 2* 0.016, 2.633 5,1 10/29 F,N,V,Y <br />
3 N ASN35: -0.318 6 -0.859, 0.016 8,5 14/29 A,N,S,T <br />
4 E GLU36: 0.737 3* 0.016, 1.214 5,1 19/29 E,G,K,Q,S,T <br />
5 M MET37: 0.793 3* 0.016, 1.214 5,1 19/29 A,E,I,L,M,Q,T <br />
6 L LEU38: -1.329 9 -1.588,-1.223 9,9 28/29 L <br />
7 Q GLN39: -0.531 7 -0.859,-0.210 8,6 28/29 K,Q,R <br />
8 S SER40: 2.423 1 2.633, 2.633 1,1 28/29 D,E,K,N,Q,R,S,T <br />
9 A ALA41: 0.058 5 -0.403, 0.294 6,4 28/29 A,G,I,M,N,S,T,V <br />
10 G GLY42: -1.069 8 -1.338,-0.859 9,8 28/29 D,G <br />
11 L LEU43: -0.850 8 -1.223,-0.570 9,7 28/29 I,L,V <br />
12 R ARG44: -0.998 8 -1.223,-0.859 9,8 28/29 K,R <br />
13 P PRO45: 0.305 4 -0.210, 0.661 6,3 28/29 A,I,P,V,Y <br />
14 T THR46: -1.473 9 -1.588,-1.455 9,9 28/29 T <br />
15 R ARG47: 0.816 3* 0.016, 1.214 5,1 28/29 E,F,G,K,L,P,R,V <br />
16 Q GLN48: -0.961 8 -1.223,-0.721 9,7 28/29 P,Q <br />
17 R ARG49: -1.426 9 -1.588,-1.338 9,9 28/29 R <br />
18 M MET50: 0.754 3* 0.016, 1.214 5,1 28/29 E,H,I,L,M,Q,V <br />
19 A ALA51: -0.901 8 -1.223,-0.721 9,7 28/29 A,K,T,V <br />
20 L LEU52: -0.710 7 -0.986,-0.403 8,6 28/29 I,L,V <br />
21 G GLY53: -0.370 6 -0.859, 0.016 8,5 28/29 G,I,L,M <br />
22 W TRP54: 1.698 1 1.214, 2.633 1,1 28/29 A,D,E,K,N,Q,R,W <br />
23 L LEU55: 1.226 1 0.661, 2.633 3,1 28/29 A,F,I,L,M,T,V,Y <br />
24 L LEU56: -0.594 7 -0.986,-0.210 8,6 28/29 F,L,M,V <br />
25 F PHE57: 1.556 1 0.661, 2.633 3,1 28/29 D,E,F,I,K,N,Q,R,V,Y<br />
26 G GLY58: 2.434 1 2.633, 2.633 1,1 28/29 A,E,G,H,K,N,Q,S,T <br />
27 K LYS59: 0.609 3* 0.016, 1.214 5,1 28/29 A,E,H,K,P,S,T <br />
28 G GLY60: 2.294 1 2.633, 2.633 1,1 29/29 A,D,E,G,H,K,M,P,R <br />
29 A ALA61: 2.262 1 2.633, 2.633 1,1 27/29 A,C,E,G,L,M,N,Q,S,T<br />
30 R ARG62: 1.468 1 0.661, 2.633 3,1 19/29 E,H,Q,R <br />
31 H HIS63: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
32 L LEU64: 0.771 3* 0.016, 1.214 5,1 29/29 A,F,I,L,M,P,V,Y <br />
33 T THR65: -0.874 8 -1.107,-0.721 8,7 29/29 D,E,S,T <br />
34 A ALA66: -1.188 9 -1.338,-0.986 9,8 29/29 A,P,T <br />
35 E GLU67: -1.035 8 -1.338,-0.859 9,8 29/29 D,E <br />
36 M MET68: 0.707 3* 0.016, 1.214 5,1 29/29 A,D,E,H,M,S,T <br />
37 L LEU69: 0.078 5 -0.403, 0.294 6,4 29/29 C,I,L,V <br />
38 Y TYR70: -0.574 7 -0.986,-0.210 8,6 29/29 F,I,Y <br />
39 E GLU71: 0.157 5 -0.403, 0.661 6,3 29/29 E,G,K,M,N,Q,R <br />
40 E GLU72: 1.498 1 0.661, 2.633 3,1 29/29 A,E,H,I,K,L,R <br />
41 A ALA73: -0.319 6 -0.721, 0.016 7,5 29/29 A,F,I,L,V <br />
42 T THR74: 1.036 2 0.294, 1.214 4,1 29/29 A,E,I,L,M,R,S,T <br />
43 L LEU75: 1.694 1 0.661, 2.633 3,1 29/29 A,D,E,F,G,L,N,P,S,V<br />
44 A ALA76: 2.302 1 2.633, 2.633 1,1 29/29 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K LYS77: 2.001 1 1.214, 2.633 1,1 29/29 D,F,G,H,K,L,N,S <br />
46 V VAL78: 0.670 3* 0.016, 1.214 5,1 29/29 C,E,L,M,P,S,V <br />
47 P PRO79: 0.328 4 -0.210, 0.661 6,3 29/29 D,E,N,P <br />
48 V VAL80: -0.744 7 -0.986,-0.570 8,7 29/29 I,M,V <br />
49 S SER81: -1.279 9 -1.455,-1.107 9,8 29/29 G,S <br />
50 L LEU82: -0.133 5 -0.570, 0.294 7,4 29/29 H,I,L,R,V <br />
51 A ALA83: -1.171 9 -1.338,-0.986 9,8 29/29 A,Q,S <br />
52 T THR84: -1.376 9 -1.588,-1.223 9,9 29/29 A,T <br />
53 V VAL85: -1.007 8 -1.223,-0.859 9,8 29/29 I,V <br />
54 Y TYR86: -1.335 9 -1.588,-1.223 9,9 29/29 Y <br />
55 N ASN87: -1.123 8 -1.338,-0.986 9,8 29/29 D,N,R <br />
56 T THR88: -0.956 8 -1.223,-0.721 9,7 29/29 N,T,V,X <br />
57 L LEU89: -1.357 9 -1.588,-1.223 9,9 29/29 L <br />
58 N ASN90: -0.647 7 -0.986,-0.403 8,6 29/29 H,K,N,R,T <br />
59 Q GLN91: -0.558 7 -0.859,-0.210 8,6 29/29 A,L,Q,V <br />
60 L LEU92: -0.570 7 -0.986,-0.210 8,6 29/29 F,L,M <br />
61 T THR93: -0.099 5 -0.570, 0.294 7,4 29/29 A,D,E,K,R,T <br />
62 D ASP94: 0.354 4 -0.210, 0.661 6,3 29/29 A,D,E,Q,R,S <br />
63 A ALA95: -0.757 7 -1.107,-0.570 8,7 29/29 A,I,M,S,V <br />
64 G GLY96: -0.841 8 -1.223,-0.570 9,7 29/29 E,G,H <br />
65 L LEU97: -0.306 6 -0.721, 0.016 7,5 29/29 I,L,M <br />
66 L LEU98: -0.712 7 -0.986,-0.403 8,6 29/29 L,V <br />
67 R ARG99: 0.384 4 -0.210, 0.661 6,3 29/29 I,K,L,Q,R,S,T,V <br />
68 Q GLN100: -0.238 6 -0.570, 0.016 7,5 29/29 E,K,Q,R,S <br />
69 V VAL101: -0.147 5 -0.570, 0.294 7,4 29/29 H,I,L,N,S,V <br />
70 S SER102: 0.078 5 -0.403, 0.294 6,4 29/29 D,H,N,P,Q,S,T <br />
71 V VAL103: 0.145 5 -0.403, 0.661 6,3 29/29 F,L,P,V,Y <br />
72 D ASP104: 0.881 2 0.294, 1.214 4,1 29/29 A,D,E,G,S,T <br />
73 G GLY105: 0.110 5 -0.403, 0.661 6,3 29/29 D,E,G,S,T <br />
74 T THR106: -0.006 5 -0.403, 0.294 6,4 29/29 A,D,G,N,S,T <br />
75 K LYS107: 0.077 5 -0.403, 0.294 6,4 29/29 G,H,K,S,V <br />
76 T THR108: -0.179 6 -0.570, 0.016 7,5 29/29 A,K,S,T <br />
77 Y TYR109: -0.415 6 -0.721,-0.210 7,6 29/29 H,I,K,R,V,Y <br />
78 F PHE110: -0.368 6 -0.721, 0.016 7,5 29/29 F,Y <br />
79 D ASP111: -1.082 8 -1.338,-0.859 9,8 29/29 D,E <br />
80 T THR112: -0.448 6 -0.859,-0.210 8,6 29/29 F,L,S,T <br />
81 N ASN113: 0.772 3 0.294, 1.214 4,1 29/29 A,D,N,R,S,T,V <br />
82 V VAL114: 0.383 4* -0.570, 1.214 7,1 2/29 Q,V <br />
83 T THR115: 2.165 1 1.214, 2.633 1,1 23/29 D,E,K,N,P,Q,T,V <br />
84 T THR116: 1.506 1 0.661, 2.633 3,1 29/29 D,G,K,L,N,Q,S,T <br />
85 H HIS117: 1.472 1 0.661, 2.633 3,1 29/29 D,E,G,H,K,P,S <br />
86 H HIS118: -0.825 8 -1.107,-0.570 8,7 29/29 D,E,H,N <br />
87 H HIS119: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
88 Y TYR120: -0.874 8 -1.107,-0.721 8,7 29/29 D,H,Y <br />
89 Y TYR121: -1.329 9 -1.455,-1.223 9,9 29/29 H,Y <br />
90 L LEU122: 1.136 2 0.294, 1.214 4,1 25/29 A,I,L,M,V <br />
91 E GLU123: 1.417 1 0.661, 2.633 3,1 18/29 E,K,L,M,T,V <br />
92 N ASN124: 0.930 2* 0.016, 1.214 5,1 18/29 D,E,K,N,Q,V <br />
93 S SER125: -0.572 7 -0.986,-0.210 8,6 18/29 C,S,T <br />
94 H HIS126: -0.108 5 -0.721, 0.294 7,4 18/29 G,H,N,S <br />
95 E GLU127: -0.355 6 -0.859, 0.016 8,5 18/29 E,K,T <br />
96 L LEU128: -0.913 8 -1.223,-0.721 9,7 18/29 I,L,V <br />
97 V VAL129: -0.280 6 -0.721, 0.016 7,5 18/29 F,I,T,V <br />
98 D ASP130: -1.063 8 -1.338,-0.859 9,8 18/29 D,E <br />
99 I ILE131: -0.905 8 -1.223,-0.721 9,7 18/29 F,I <br />
100 E GLU132: 1.739 1 1.214, 2.633 1,1 18/29 E,H,K,M,Q,S,T <br />
101 D ASP133: -0.254 6 -0.721, 0.016 7,5 18/29 D,N,S,Y <br />
102 P PRO134: -0.193 6 -0.721, 0.294 7,4 18/29 A,E,N,P <br />
103 H HIS135: 1.561 1 0.661, 2.633 3,1 16/29 D,E,G,H,I,Q,V <br />
104 L LEU136: -1.023 8 -1.338,-0.859 9,8 16/29 I,L <br />
105 A ALA137: 0.666 3* -0.210, 1.214 6,1 7/29 A,K,Q <br />
106 L LEU138: 0.051 5* -0.721, 0.661 7,3 7/29 L,R <br />
107 S SER139: -0.624 7 -1.107,-0.210 8,6 7/29 Q,S <br />
108 K LYS140: 0.661 3* -0.210, 1.214 6,1 7/29 D,K,R <br />
109 M MET141: 0.164 4* -0.570, 0.661 7,3 7/29 E,K,M <br />
110 P PRO142: -0.492 7 -0.986,-0.210 8,6 7/29 I,P <br />
111 E GLU143: 0.243 4* -0.570, 0.661 7,3 7/29 A,E,S,V <br />
112 V VAL144: 0.835 2* 0.016, 1.214 5,1 7/29 A,E,R,V <br />
113 P PRO145: 0.779 3* 0.016, 1.214 5,1 7/29 E,K,P,Q <br />
114 E GLU146: 1.555 1 0.661, 2.633 3,1 7/29 E,H,N,R,Y <br />
115 G GLY147: -0.540 7 -1.107,-0.210 8,6 7/29 G,N <br />
116 Y TYR148: 1.072 2 0.294, 2.633 4,1 7/29 F,I,V,Y <br />
117 E GLU149: -0.017 5* -0.859, 0.661 8,3 5/29 E,R <br />
118 I ILE150: -0.332 6* -0.986, 0.016 8,5 5/29 I,L <br />
119 A ALA151: -0.318 6* -0.986, 0.016 8,5 3/29 A,V <br />
120 R ARG152: 0.307 4* -0.570, 1.214 7,1 3/29 D,R <br />
121 I ILE153: 0.330 4* -0.570, 1.214 7,1 3/29 H,I <br />
122 D ASP154: -0.429 6* -1.107, 0.016 8,5 3/29 D,N <br />
123 M MET155: -0.296 6* -0.986, 0.016 8,5 3/29 L,M <br />
124 V VAL156: -0.946 8* -1.455,-0.721 9,7 3/29 V <br />
125 V VAL157: -0.137 5* -0.859, 0.294 8,4 3/29 L,V <br />
126 R ARG158: 0.277 4* -0.570, 1.214 7,1 3/29 R,Y <br />
127 L LEU159: -0.174 6* -0.859, 0.294 8,4 3/29 L,V <br />
128 R ARG160: -0.959 8* -1.455,-0.721 9,7 3/29 R <br />
129 K LYS161: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
130 K LYS162: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
131 R ARG163: -0.419 6* -1.107, 0.016 8,5 3/29 K,R <br />
<br />
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<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
----<br />
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The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
[[image:irr.png|400px]]<br />
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==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951399User:Adam Meade/Sandbox 12009-04-27T14:55:39Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
----<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
----<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Function of Irr'''<br />
----<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Chemical and Physical Properties of Irr'''<br />
----<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
'''Evolution of Irr/Fur'''<br />
----<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- 3LATOM: The ATOM derived sequence in three letter code, including the AA's positions as they appear in the PDB file and the chain identifier.<br />
<br />
- SCORE: The normalized conservation scores.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- CONFIDENCE INTERVAL: When using the bayesian method for calculating rates, a confidence interval is assigned to each of the inferred evolutionary conservation scores.<br />
<br />
- CONFIDENCE INTERVAL COLORS: When using the bayesian method for calculating rates. The color scale representing the lower and upper bounds of the confidence interval.<br />
<br />
- MSA DATA: The number of aligned sequences having an amino acid (non-gapped) from the overall number of sequences at each position.<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ 3LATOM SCORE COLOR CONFIDENCE INTERVAL CONFIDENCE INTERVAL COLORS MSA DATA RESIDUE VARIETY<br />
(normalized) <br />
1 D ASP33: -1.189 9 -1.455,-0.986 9,8 10/29 D <br />
2 V VAL34: 0.979 2* 0.016, 2.633 5,1 10/29 F,N,V,Y <br />
3 N ASN35: -0.318 6 -0.859, 0.016 8,5 14/29 A,N,S,T <br />
4 E GLU36: 0.737 3* 0.016, 1.214 5,1 19/29 E,G,K,Q,S,T <br />
5 M MET37: 0.793 3* 0.016, 1.214 5,1 19/29 A,E,I,L,M,Q,T <br />
6 L LEU38: -1.329 9 -1.588,-1.223 9,9 28/29 L <br />
7 Q GLN39: -0.531 7 -0.859,-0.210 8,6 28/29 K,Q,R <br />
8 S SER40: 2.423 1 2.633, 2.633 1,1 28/29 D,E,K,N,Q,R,S,T <br />
9 A ALA41: 0.058 5 -0.403, 0.294 6,4 28/29 A,G,I,M,N,S,T,V <br />
10 G GLY42: -1.069 8 -1.338,-0.859 9,8 28/29 D,G <br />
11 L LEU43: -0.850 8 -1.223,-0.570 9,7 28/29 I,L,V <br />
12 R ARG44: -0.998 8 -1.223,-0.859 9,8 28/29 K,R <br />
13 P PRO45: 0.305 4 -0.210, 0.661 6,3 28/29 A,I,P,V,Y <br />
14 T THR46: -1.473 9 -1.588,-1.455 9,9 28/29 T <br />
15 R ARG47: 0.816 3* 0.016, 1.214 5,1 28/29 E,F,G,K,L,P,R,V <br />
16 Q GLN48: -0.961 8 -1.223,-0.721 9,7 28/29 P,Q <br />
17 R ARG49: -1.426 9 -1.588,-1.338 9,9 28/29 R <br />
18 M MET50: 0.754 3* 0.016, 1.214 5,1 28/29 E,H,I,L,M,Q,V <br />
19 A ALA51: -0.901 8 -1.223,-0.721 9,7 28/29 A,K,T,V <br />
20 L LEU52: -0.710 7 -0.986,-0.403 8,6 28/29 I,L,V <br />
21 G GLY53: -0.370 6 -0.859, 0.016 8,5 28/29 G,I,L,M <br />
22 W TRP54: 1.698 1 1.214, 2.633 1,1 28/29 A,D,E,K,N,Q,R,W <br />
23 L LEU55: 1.226 1 0.661, 2.633 3,1 28/29 A,F,I,L,M,T,V,Y <br />
24 L LEU56: -0.594 7 -0.986,-0.210 8,6 28/29 F,L,M,V <br />
25 F PHE57: 1.556 1 0.661, 2.633 3,1 28/29 D,E,F,I,K,N,Q,R,V,Y<br />
26 G GLY58: 2.434 1 2.633, 2.633 1,1 28/29 A,E,G,H,K,N,Q,S,T <br />
27 K LYS59: 0.609 3* 0.016, 1.214 5,1 28/29 A,E,H,K,P,S,T <br />
28 G GLY60: 2.294 1 2.633, 2.633 1,1 29/29 A,D,E,G,H,K,M,P,R <br />
29 A ALA61: 2.262 1 2.633, 2.633 1,1 27/29 A,C,E,G,L,M,N,Q,S,T<br />
30 R ARG62: 1.468 1 0.661, 2.633 3,1 19/29 E,H,Q,R <br />
31 H HIS63: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
32 L LEU64: 0.771 3* 0.016, 1.214 5,1 29/29 A,F,I,L,M,P,V,Y <br />
33 T THR65: -0.874 8 -1.107,-0.721 8,7 29/29 D,E,S,T <br />
34 A ALA66: -1.188 9 -1.338,-0.986 9,8 29/29 A,P,T <br />
35 E GLU67: -1.035 8 -1.338,-0.859 9,8 29/29 D,E <br />
36 M MET68: 0.707 3* 0.016, 1.214 5,1 29/29 A,D,E,H,M,S,T <br />
37 L LEU69: 0.078 5 -0.403, 0.294 6,4 29/29 C,I,L,V <br />
38 Y TYR70: -0.574 7 -0.986,-0.210 8,6 29/29 F,I,Y <br />
39 E GLU71: 0.157 5 -0.403, 0.661 6,3 29/29 E,G,K,M,N,Q,R <br />
40 E GLU72: 1.498 1 0.661, 2.633 3,1 29/29 A,E,H,I,K,L,R <br />
41 A ALA73: -0.319 6 -0.721, 0.016 7,5 29/29 A,F,I,L,V <br />
42 T THR74: 1.036 2 0.294, 1.214 4,1 29/29 A,E,I,L,M,R,S,T <br />
43 L LEU75: 1.694 1 0.661, 2.633 3,1 29/29 A,D,E,F,G,L,N,P,S,V<br />
44 A ALA76: 2.302 1 2.633, 2.633 1,1 29/29 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K LYS77: 2.001 1 1.214, 2.633 1,1 29/29 D,F,G,H,K,L,N,S <br />
46 V VAL78: 0.670 3* 0.016, 1.214 5,1 29/29 C,E,L,M,P,S,V <br />
47 P PRO79: 0.328 4 -0.210, 0.661 6,3 29/29 D,E,N,P <br />
48 V VAL80: -0.744 7 -0.986,-0.570 8,7 29/29 I,M,V <br />
49 S SER81: -1.279 9 -1.455,-1.107 9,8 29/29 G,S <br />
50 L LEU82: -0.133 5 -0.570, 0.294 7,4 29/29 H,I,L,R,V <br />
51 A ALA83: -1.171 9 -1.338,-0.986 9,8 29/29 A,Q,S <br />
52 T THR84: -1.376 9 -1.588,-1.223 9,9 29/29 A,T <br />
53 V VAL85: -1.007 8 -1.223,-0.859 9,8 29/29 I,V <br />
54 Y TYR86: -1.335 9 -1.588,-1.223 9,9 29/29 Y <br />
55 N ASN87: -1.123 8 -1.338,-0.986 9,8 29/29 D,N,R <br />
56 T THR88: -0.956 8 -1.223,-0.721 9,7 29/29 N,T,V,X <br />
57 L LEU89: -1.357 9 -1.588,-1.223 9,9 29/29 L <br />
58 N ASN90: -0.647 7 -0.986,-0.403 8,6 29/29 H,K,N,R,T <br />
59 Q GLN91: -0.558 7 -0.859,-0.210 8,6 29/29 A,L,Q,V <br />
60 L LEU92: -0.570 7 -0.986,-0.210 8,6 29/29 F,L,M <br />
61 T THR93: -0.099 5 -0.570, 0.294 7,4 29/29 A,D,E,K,R,T <br />
62 D ASP94: 0.354 4 -0.210, 0.661 6,3 29/29 A,D,E,Q,R,S <br />
63 A ALA95: -0.757 7 -1.107,-0.570 8,7 29/29 A,I,M,S,V <br />
64 G GLY96: -0.841 8 -1.223,-0.570 9,7 29/29 E,G,H <br />
65 L LEU97: -0.306 6 -0.721, 0.016 7,5 29/29 I,L,M <br />
66 L LEU98: -0.712 7 -0.986,-0.403 8,6 29/29 L,V <br />
67 R ARG99: 0.384 4 -0.210, 0.661 6,3 29/29 I,K,L,Q,R,S,T,V <br />
68 Q GLN100: -0.238 6 -0.570, 0.016 7,5 29/29 E,K,Q,R,S <br />
69 V VAL101: -0.147 5 -0.570, 0.294 7,4 29/29 H,I,L,N,S,V <br />
70 S SER102: 0.078 5 -0.403, 0.294 6,4 29/29 D,H,N,P,Q,S,T <br />
71 V VAL103: 0.145 5 -0.403, 0.661 6,3 29/29 F,L,P,V,Y <br />
72 D ASP104: 0.881 2 0.294, 1.214 4,1 29/29 A,D,E,G,S,T <br />
73 G GLY105: 0.110 5 -0.403, 0.661 6,3 29/29 D,E,G,S,T <br />
74 T THR106: -0.006 5 -0.403, 0.294 6,4 29/29 A,D,G,N,S,T <br />
75 K LYS107: 0.077 5 -0.403, 0.294 6,4 29/29 G,H,K,S,V <br />
76 T THR108: -0.179 6 -0.570, 0.016 7,5 29/29 A,K,S,T <br />
77 Y TYR109: -0.415 6 -0.721,-0.210 7,6 29/29 H,I,K,R,V,Y <br />
78 F PHE110: -0.368 6 -0.721, 0.016 7,5 29/29 F,Y <br />
79 D ASP111: -1.082 8 -1.338,-0.859 9,8 29/29 D,E <br />
80 T THR112: -0.448 6 -0.859,-0.210 8,6 29/29 F,L,S,T <br />
81 N ASN113: 0.772 3 0.294, 1.214 4,1 29/29 A,D,N,R,S,T,V <br />
82 V VAL114: 0.383 4* -0.570, 1.214 7,1 2/29 Q,V <br />
83 T THR115: 2.165 1 1.214, 2.633 1,1 23/29 D,E,K,N,P,Q,T,V <br />
84 T THR116: 1.506 1 0.661, 2.633 3,1 29/29 D,G,K,L,N,Q,S,T <br />
85 H HIS117: 1.472 1 0.661, 2.633 3,1 29/29 D,E,G,H,K,P,S <br />
86 H HIS118: -0.825 8 -1.107,-0.570 8,7 29/29 D,E,H,N <br />
87 H HIS119: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
88 Y TYR120: -0.874 8 -1.107,-0.721 8,7 29/29 D,H,Y <br />
89 Y TYR121: -1.329 9 -1.455,-1.223 9,9 29/29 H,Y <br />
90 L LEU122: 1.136 2 0.294, 1.214 4,1 25/29 A,I,L,M,V <br />
91 E GLU123: 1.417 1 0.661, 2.633 3,1 18/29 E,K,L,M,T,V <br />
92 N ASN124: 0.930 2* 0.016, 1.214 5,1 18/29 D,E,K,N,Q,V <br />
93 S SER125: -0.572 7 -0.986,-0.210 8,6 18/29 C,S,T <br />
94 H HIS126: -0.108 5 -0.721, 0.294 7,4 18/29 G,H,N,S <br />
95 E GLU127: -0.355 6 -0.859, 0.016 8,5 18/29 E,K,T <br />
96 L LEU128: -0.913 8 -1.223,-0.721 9,7 18/29 I,L,V <br />
97 V VAL129: -0.280 6 -0.721, 0.016 7,5 18/29 F,I,T,V <br />
98 D ASP130: -1.063 8 -1.338,-0.859 9,8 18/29 D,E <br />
99 I ILE131: -0.905 8 -1.223,-0.721 9,7 18/29 F,I <br />
100 E GLU132: 1.739 1 1.214, 2.633 1,1 18/29 E,H,K,M,Q,S,T <br />
101 D ASP133: -0.254 6 -0.721, 0.016 7,5 18/29 D,N,S,Y <br />
102 P PRO134: -0.193 6 -0.721, 0.294 7,4 18/29 A,E,N,P <br />
103 H HIS135: 1.561 1 0.661, 2.633 3,1 16/29 D,E,G,H,I,Q,V <br />
104 L LEU136: -1.023 8 -1.338,-0.859 9,8 16/29 I,L <br />
105 A ALA137: 0.666 3* -0.210, 1.214 6,1 7/29 A,K,Q <br />
106 L LEU138: 0.051 5* -0.721, 0.661 7,3 7/29 L,R <br />
107 S SER139: -0.624 7 -1.107,-0.210 8,6 7/29 Q,S <br />
108 K LYS140: 0.661 3* -0.210, 1.214 6,1 7/29 D,K,R <br />
109 M MET141: 0.164 4* -0.570, 0.661 7,3 7/29 E,K,M <br />
110 P PRO142: -0.492 7 -0.986,-0.210 8,6 7/29 I,P <br />
111 E GLU143: 0.243 4* -0.570, 0.661 7,3 7/29 A,E,S,V <br />
112 V VAL144: 0.835 2* 0.016, 1.214 5,1 7/29 A,E,R,V <br />
113 P PRO145: 0.779 3* 0.016, 1.214 5,1 7/29 E,K,P,Q <br />
114 E GLU146: 1.555 1 0.661, 2.633 3,1 7/29 E,H,N,R,Y <br />
115 G GLY147: -0.540 7 -1.107,-0.210 8,6 7/29 G,N <br />
116 Y TYR148: 1.072 2 0.294, 2.633 4,1 7/29 F,I,V,Y <br />
117 E GLU149: -0.017 5* -0.859, 0.661 8,3 5/29 E,R <br />
118 I ILE150: -0.332 6* -0.986, 0.016 8,5 5/29 I,L <br />
119 A ALA151: -0.318 6* -0.986, 0.016 8,5 3/29 A,V <br />
120 R ARG152: 0.307 4* -0.570, 1.214 7,1 3/29 D,R <br />
121 I ILE153: 0.330 4* -0.570, 1.214 7,1 3/29 H,I <br />
122 D ASP154: -0.429 6* -1.107, 0.016 8,5 3/29 D,N <br />
123 M MET155: -0.296 6* -0.986, 0.016 8,5 3/29 L,M <br />
124 V VAL156: -0.946 8* -1.455,-0.721 9,7 3/29 V <br />
125 V VAL157: -0.137 5* -0.859, 0.294 8,4 3/29 L,V <br />
126 R ARG158: 0.277 4* -0.570, 1.214 7,1 3/29 R,Y <br />
127 L LEU159: -0.174 6* -0.859, 0.294 8,4 3/29 L,V <br />
128 R ARG160: -0.959 8* -1.455,-0.721 9,7 3/29 R <br />
129 K LYS161: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
130 K LYS162: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
131 R ARG163: -0.419 6* -1.107, 0.016 8,5 3/29 K,R <br />
<br />
<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
----<br />
<br />
[[image:irr.png|400px]]<br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
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==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=951047User:Adam Meade/Sandbox 12009-04-26T17:40:10Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
----<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
----<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Function of Irr'''<br />
----<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Chemical and Physical Properties of Irr'''<br />
----<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
'''Evolution of Irr/Fur'''<br />
----<br />
Amino Acid Conservation Scores<br />
----<br />
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.<br />
<br />
- POS: The position of the AA in the SEQRES derived sequence.<br />
<br />
- SEQ: The SEQRES derived sequence in one letter code.<br />
<br />
- 3LATOM: The ATOM derived sequence in three letter code, including the AA's positions as they appear in the PDB file and the chain identifier.<br />
<br />
- SCORE: The normalized conservation scores.<br />
<br />
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).<br />
<br />
- CONFIDENCE INTERVAL: When using the bayesian method for calculating rates, a confidence interval is assigned to each of the inferred evolutionary conservation scores.<br />
<br />
- CONFIDENCE INTERVAL COLORS: When using the bayesian method for calculating rates. The color scale representing the lower and upper bounds of the confidence interval.<br />
<br />
- MSA DATA: The number of aligned sequences having an amino acid (non-gapped) from the overall number of sequences at each position.<br />
<br />
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.<br />
<br />
<br />
<br />
POS SEQ 3LATOM SCORE COLOR CONFIDENCE INTERVAL CONFIDENCE INTERVAL COLORS MSA DATA RESIDUE VARIETY<br />
(normalized) <br />
1 D ASP33: -1.189 9 -1.455,-0.986 9,8 10/29 D <br />
2 V VAL34: 0.979 2* 0.016, 2.633 5,1 10/29 F,N,V,Y <br />
3 N ASN35: -0.318 6 -0.859, 0.016 8,5 14/29 A,N,S,T <br />
4 E GLU36: 0.737 3* 0.016, 1.214 5,1 19/29 E,G,K,Q,S,T <br />
5 M MET37: 0.793 3* 0.016, 1.214 5,1 19/29 A,E,I,L,M,Q,T <br />
6 L LEU38: -1.329 9 -1.588,-1.223 9,9 28/29 L <br />
7 Q GLN39: -0.531 7 -0.859,-0.210 8,6 28/29 K,Q,R <br />
8 S SER40: 2.423 1 2.633, 2.633 1,1 28/29 D,E,K,N,Q,R,S,T <br />
9 A ALA41: 0.058 5 -0.403, 0.294 6,4 28/29 A,G,I,M,N,S,T,V <br />
10 G GLY42: -1.069 8 -1.338,-0.859 9,8 28/29 D,G <br />
11 L LEU43: -0.850 8 -1.223,-0.570 9,7 28/29 I,L,V <br />
12 R ARG44: -0.998 8 -1.223,-0.859 9,8 28/29 K,R <br />
13 P PRO45: 0.305 4 -0.210, 0.661 6,3 28/29 A,I,P,V,Y <br />
14 T THR46: -1.473 9 -1.588,-1.455 9,9 28/29 T <br />
15 R ARG47: 0.816 3* 0.016, 1.214 5,1 28/29 E,F,G,K,L,P,R,V <br />
16 Q GLN48: -0.961 8 -1.223,-0.721 9,7 28/29 P,Q <br />
17 R ARG49: -1.426 9 -1.588,-1.338 9,9 28/29 R <br />
18 M MET50: 0.754 3* 0.016, 1.214 5,1 28/29 E,H,I,L,M,Q,V <br />
19 A ALA51: -0.901 8 -1.223,-0.721 9,7 28/29 A,K,T,V <br />
20 L LEU52: -0.710 7 -0.986,-0.403 8,6 28/29 I,L,V <br />
21 G GLY53: -0.370 6 -0.859, 0.016 8,5 28/29 G,I,L,M <br />
22 W TRP54: 1.698 1 1.214, 2.633 1,1 28/29 A,D,E,K,N,Q,R,W <br />
23 L LEU55: 1.226 1 0.661, 2.633 3,1 28/29 A,F,I,L,M,T,V,Y <br />
24 L LEU56: -0.594 7 -0.986,-0.210 8,6 28/29 F,L,M,V <br />
25 F PHE57: 1.556 1 0.661, 2.633 3,1 28/29 D,E,F,I,K,N,Q,R,V,Y<br />
26 G GLY58: 2.434 1 2.633, 2.633 1,1 28/29 A,E,G,H,K,N,Q,S,T <br />
27 K LYS59: 0.609 3* 0.016, 1.214 5,1 28/29 A,E,H,K,P,S,T <br />
28 G GLY60: 2.294 1 2.633, 2.633 1,1 29/29 A,D,E,G,H,K,M,P,R <br />
29 A ALA61: 2.262 1 2.633, 2.633 1,1 27/29 A,C,E,G,L,M,N,Q,S,T<br />
30 R ARG62: 1.468 1 0.661, 2.633 3,1 19/29 E,H,Q,R <br />
31 H HIS63: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
32 L LEU64: 0.771 3* 0.016, 1.214 5,1 29/29 A,F,I,L,M,P,V,Y <br />
33 T THR65: -0.874 8 -1.107,-0.721 8,7 29/29 D,E,S,T <br />
34 A ALA66: -1.188 9 -1.338,-0.986 9,8 29/29 A,P,T <br />
35 E GLU67: -1.035 8 -1.338,-0.859 9,8 29/29 D,E <br />
36 M MET68: 0.707 3* 0.016, 1.214 5,1 29/29 A,D,E,H,M,S,T <br />
37 L LEU69: 0.078 5 -0.403, 0.294 6,4 29/29 C,I,L,V <br />
38 Y TYR70: -0.574 7 -0.986,-0.210 8,6 29/29 F,I,Y <br />
39 E GLU71: 0.157 5 -0.403, 0.661 6,3 29/29 E,G,K,M,N,Q,R <br />
40 E GLU72: 1.498 1 0.661, 2.633 3,1 29/29 A,E,H,I,K,L,R <br />
41 A ALA73: -0.319 6 -0.721, 0.016 7,5 29/29 A,F,I,L,V <br />
42 T THR74: 1.036 2 0.294, 1.214 4,1 29/29 A,E,I,L,M,R,S,T <br />
43 L LEU75: 1.694 1 0.661, 2.633 3,1 29/29 A,D,E,F,G,L,N,P,S,V<br />
44 A ALA76: 2.302 1 2.633, 2.633 1,1 29/29 A,D,E,I,K,L,M,P,Q,R,S<br />
45 K LYS77: 2.001 1 1.214, 2.633 1,1 29/29 D,F,G,H,K,L,N,S <br />
46 V VAL78: 0.670 3* 0.016, 1.214 5,1 29/29 C,E,L,M,P,S,V <br />
47 P PRO79: 0.328 4 -0.210, 0.661 6,3 29/29 D,E,N,P <br />
48 V VAL80: -0.744 7 -0.986,-0.570 8,7 29/29 I,M,V <br />
49 S SER81: -1.279 9 -1.455,-1.107 9,8 29/29 G,S <br />
50 L LEU82: -0.133 5 -0.570, 0.294 7,4 29/29 H,I,L,R,V <br />
51 A ALA83: -1.171 9 -1.338,-0.986 9,8 29/29 A,Q,S <br />
52 T THR84: -1.376 9 -1.588,-1.223 9,9 29/29 A,T <br />
53 V VAL85: -1.007 8 -1.223,-0.859 9,8 29/29 I,V <br />
54 Y TYR86: -1.335 9 -1.588,-1.223 9,9 29/29 Y <br />
55 N ASN87: -1.123 8 -1.338,-0.986 9,8 29/29 D,N,R <br />
56 T THR88: -0.956 8 -1.223,-0.721 9,7 29/29 N,T,V,X <br />
57 L LEU89: -1.357 9 -1.588,-1.223 9,9 29/29 L <br />
58 N ASN90: -0.647 7 -0.986,-0.403 8,6 29/29 H,K,N,R,T <br />
59 Q GLN91: -0.558 7 -0.859,-0.210 8,6 29/29 A,L,Q,V <br />
60 L LEU92: -0.570 7 -0.986,-0.210 8,6 29/29 F,L,M <br />
61 T THR93: -0.099 5 -0.570, 0.294 7,4 29/29 A,D,E,K,R,T <br />
62 D ASP94: 0.354 4 -0.210, 0.661 6,3 29/29 A,D,E,Q,R,S <br />
63 A ALA95: -0.757 7 -1.107,-0.570 8,7 29/29 A,I,M,S,V <br />
64 G GLY96: -0.841 8 -1.223,-0.570 9,7 29/29 E,G,H <br />
65 L LEU97: -0.306 6 -0.721, 0.016 7,5 29/29 I,L,M <br />
66 L LEU98: -0.712 7 -0.986,-0.403 8,6 29/29 L,V <br />
67 R ARG99: 0.384 4 -0.210, 0.661 6,3 29/29 I,K,L,Q,R,S,T,V <br />
68 Q GLN100: -0.238 6 -0.570, 0.016 7,5 29/29 E,K,Q,R,S <br />
69 V VAL101: -0.147 5 -0.570, 0.294 7,4 29/29 H,I,L,N,S,V <br />
70 S SER102: 0.078 5 -0.403, 0.294 6,4 29/29 D,H,N,P,Q,S,T <br />
71 V VAL103: 0.145 5 -0.403, 0.661 6,3 29/29 F,L,P,V,Y <br />
72 D ASP104: 0.881 2 0.294, 1.214 4,1 29/29 A,D,E,G,S,T <br />
73 G GLY105: 0.110 5 -0.403, 0.661 6,3 29/29 D,E,G,S,T <br />
74 T THR106: -0.006 5 -0.403, 0.294 6,4 29/29 A,D,G,N,S,T <br />
75 K LYS107: 0.077 5 -0.403, 0.294 6,4 29/29 G,H,K,S,V <br />
76 T THR108: -0.179 6 -0.570, 0.016 7,5 29/29 A,K,S,T <br />
77 Y TYR109: -0.415 6 -0.721,-0.210 7,6 29/29 H,I,K,R,V,Y <br />
78 F PHE110: -0.368 6 -0.721, 0.016 7,5 29/29 F,Y <br />
79 D ASP111: -1.082 8 -1.338,-0.859 9,8 29/29 D,E <br />
80 T THR112: -0.448 6 -0.859,-0.210 8,6 29/29 F,L,S,T <br />
81 N ASN113: 0.772 3 0.294, 1.214 4,1 29/29 A,D,N,R,S,T,V <br />
82 V VAL114: 0.383 4* -0.570, 1.214 7,1 2/29 Q,V <br />
83 T THR115: 2.165 1 1.214, 2.633 1,1 23/29 D,E,K,N,P,Q,T,V <br />
84 T THR116: 1.506 1 0.661, 2.633 3,1 29/29 D,G,K,L,N,Q,S,T <br />
85 H HIS117: 1.472 1 0.661, 2.633 3,1 29/29 D,E,G,H,K,P,S <br />
86 H HIS118: -0.825 8 -1.107,-0.570 8,7 29/29 D,E,H,N <br />
87 H HIS119: -1.467 9 -1.588,-1.455 9,9 29/29 H <br />
88 Y TYR120: -0.874 8 -1.107,-0.721 8,7 29/29 D,H,Y <br />
89 Y TYR121: -1.329 9 -1.455,-1.223 9,9 29/29 H,Y <br />
90 L LEU122: 1.136 2 0.294, 1.214 4,1 25/29 A,I,L,M,V <br />
91 E GLU123: 1.417 1 0.661, 2.633 3,1 18/29 E,K,L,M,T,V <br />
92 N ASN124: 0.930 2* 0.016, 1.214 5,1 18/29 D,E,K,N,Q,V <br />
93 S SER125: -0.572 7 -0.986,-0.210 8,6 18/29 C,S,T <br />
94 H HIS126: -0.108 5 -0.721, 0.294 7,4 18/29 G,H,N,S <br />
95 E GLU127: -0.355 6 -0.859, 0.016 8,5 18/29 E,K,T <br />
96 L LEU128: -0.913 8 -1.223,-0.721 9,7 18/29 I,L,V <br />
97 V VAL129: -0.280 6 -0.721, 0.016 7,5 18/29 F,I,T,V <br />
98 D ASP130: -1.063 8 -1.338,-0.859 9,8 18/29 D,E <br />
99 I ILE131: -0.905 8 -1.223,-0.721 9,7 18/29 F,I <br />
100 E GLU132: 1.739 1 1.214, 2.633 1,1 18/29 E,H,K,M,Q,S,T <br />
101 D ASP133: -0.254 6 -0.721, 0.016 7,5 18/29 D,N,S,Y <br />
102 P PRO134: -0.193 6 -0.721, 0.294 7,4 18/29 A,E,N,P <br />
103 H HIS135: 1.561 1 0.661, 2.633 3,1 16/29 D,E,G,H,I,Q,V <br />
104 L LEU136: -1.023 8 -1.338,-0.859 9,8 16/29 I,L <br />
105 A ALA137: 0.666 3* -0.210, 1.214 6,1 7/29 A,K,Q <br />
106 L LEU138: 0.051 5* -0.721, 0.661 7,3 7/29 L,R <br />
107 S SER139: -0.624 7 -1.107,-0.210 8,6 7/29 Q,S <br />
108 K LYS140: 0.661 3* -0.210, 1.214 6,1 7/29 D,K,R <br />
109 M MET141: 0.164 4* -0.570, 0.661 7,3 7/29 E,K,M <br />
110 P PRO142: -0.492 7 -0.986,-0.210 8,6 7/29 I,P <br />
111 E GLU143: 0.243 4* -0.570, 0.661 7,3 7/29 A,E,S,V <br />
112 V VAL144: 0.835 2* 0.016, 1.214 5,1 7/29 A,E,R,V <br />
113 P PRO145: 0.779 3* 0.016, 1.214 5,1 7/29 E,K,P,Q <br />
114 E GLU146: 1.555 1 0.661, 2.633 3,1 7/29 E,H,N,R,Y <br />
115 G GLY147: -0.540 7 -1.107,-0.210 8,6 7/29 G,N <br />
116 Y TYR148: 1.072 2 0.294, 2.633 4,1 7/29 F,I,V,Y <br />
117 E GLU149: -0.017 5* -0.859, 0.661 8,3 5/29 E,R <br />
118 I ILE150: -0.332 6* -0.986, 0.016 8,5 5/29 I,L <br />
119 A ALA151: -0.318 6* -0.986, 0.016 8,5 3/29 A,V <br />
120 R ARG152: 0.307 4* -0.570, 1.214 7,1 3/29 D,R <br />
121 I ILE153: 0.330 4* -0.570, 1.214 7,1 3/29 H,I <br />
122 D ASP154: -0.429 6* -1.107, 0.016 8,5 3/29 D,N <br />
123 M MET155: -0.296 6* -0.986, 0.016 8,5 3/29 L,M <br />
124 V VAL156: -0.946 8* -1.455,-0.721 9,7 3/29 V <br />
125 V VAL157: -0.137 5* -0.859, 0.294 8,4 3/29 L,V <br />
126 R ARG158: 0.277 4* -0.570, 1.214 7,1 3/29 R,Y <br />
127 L LEU159: -0.174 6* -0.859, 0.294 8,4 3/29 L,V <br />
128 R ARG160: -0.959 8* -1.455,-0.721 9,7 3/29 R <br />
129 K LYS161: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
130 K LYS162: -0.914 8* -1.455,-0.721 9,7 3/29 K <br />
131 R ARG163: -0.419 6* -1.107, 0.016 8,5 3/29 K,R <br />
<br />
<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
----<br />
Go to polyview 3d, select "secondary structures" for coloring mode and re-upload<br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
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==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948755User:Adam Meade/Sandbox 12009-04-20T15:47:47Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
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<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Function of Irr'''<br />
<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Chemical and Physical Properties of Irr'''<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|-<br />
! align="center"| Glu (E)<br />
| align="center"| 11 || align="center"| 6.7%<br />
|-<br />
! align="center"| Gly (G)<br />
| align="center"| 9 || align="center"| 5.5%<br />
|-<br />
! align="center"| His (H)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Ile (I)<br />
| align="center"| 3 || align="center"| 1.8%<br />
|-<br />
! align="center"| Leu (L)<br />
| align="center"| 21 || align="center"| 12.9%<br />
|-<br />
! align="center"| Lys (K)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Met (M)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Phe (F)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Pro (P)<br />
| align="center"| 8 || align="center"| 4.9%<br />
|-<br />
! align="center"| Ser (S)<br />
| align="center"| 7 || align="center"| 4.3%<br />
|-<br />
! align="center"| Thr (T)<br />
| align="center"| 13 || align="center"| 8.0%<br />
|-<br />
! align="center"| Trp (W)<br />
| align="center"| 2 || align="center"| 1.2%<br />
|-<br />
! align="center"| Tyr (Y)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Val (V)<br />
| align="center"| 12 || align="center"| 7.4%<br />
|-<br />
! align="center"| Pyl (O)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|-<br />
! align="center"| Sec (U)<br />
| align="center"| 0 || align="center"| 0.0%<br />
|}<br />
<br />
<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
<br />
<br />
'''Evolution of Irr/Fur'''<br />
<br />
Go to top 5 on Rasmol, put in amino acid sequence and find domain conservations, anything related to Irr/Fur in the past (conserf). Amino acid conservation scores tell you what aa are found in positions in related aa.<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
Go to polyview 3d, select "secondary structures" for coloring mode and re-upload<br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948754User:Adam Meade/Sandbox 12009-04-20T15:42:14Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Function of Irr'''<br />
<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Chemical and Physical Properties of Irr'''<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Amino Acid !! Number present !! Percentage of total present<br />
|-<br />
! align="center"| Ala (A)<br />
| align="center"| 15 || align="center"| 9.2%<br />
|-<br />
! align="center"| Arg (R)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Asn (N)<br />
| align="center"| 6 || align="center"| 3.7%<br />
|-<br />
! align="center"| Asp (D)<br />
| align="center"| 10 || align="center"| 6.1%<br />
|-<br />
! align="center"| Cys (C)<br />
| align="center"| 1 || align="center"| 0.6%<br />
|-<br />
! align="center"| Gln (Q)<br />
| align="center"| 5 || align="center"| 3.1%<br />
|}<br />
<br />
<br />
Glu (E) 11 6.7%<br />
<br />
Gly (G) 9 5.5%<br />
<br />
His (H) 10 6.1%<br />
<br />
Ile (I) 3 1.8%<br />
<br />
Leu (L) 21 12.9%<br />
<br />
Lys (K) 6 3.7%<br />
<br />
Met (M) 6 3.7%<br />
<br />
Phe (F) 2 1.2%<br />
<br />
Pro (P) 8 4.9%<br />
<br />
Ser (S) 7 4.3%<br />
<br />
Thr (T) 13 8.0%<br />
<br />
Trp (W) 2 1.2%<br />
<br />
Tyr (Y) 6 3.7%<br />
<br />
Val (V) 12 7.4%<br />
<br />
Pyl (O) 0 0.0%<br />
<br />
Sec (U) 0 0.0%<br />
<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
<br />
<br />
'''Evolution of Irr/Fur'''<br />
<br />
Go to top 5 on Rasmol, put in amino acid sequence and find domain conservations, anything related to Irr/Fur in the past (conserf). Amino acid conservation scores tell you what aa are found in positions in related aa.<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
Go to polyview 3d, select "secondary structures" for coloring mode and re-upload<br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948753User:Adam Meade/Sandbox 12009-04-20T15:33:05Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Function of Irr'''<br />
<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Chemical and Physical Properties of Irr'''<br />
<br />
***Make into a table***<br />
<br />
{| border="1"<br />
|+ Amino Acid Composition<br />
! Column heading 1 !! Column heading 2 <br />
|-<br />
! Row heading 1<br />
| Cell 2 || Cell 3<br />
|-<br />
! Row heading A<br />
|Cell B<br />
|Cell C<br />
|}<br />
<br />
<br />
Ala (A) 15 9.2%<br />
<br />
Arg (R) 10 6.1%<br />
<br />
Asn (N) 6 3.7%<br />
<br />
Asp (D) 10 6.1%<br />
<br />
Cys (C) 1 0.6%<br />
<br />
Gln (Q) 5 3.1%<br />
<br />
Glu (E) 11 6.7%<br />
<br />
Gly (G) 9 5.5%<br />
<br />
His (H) 10 6.1%<br />
<br />
Ile (I) 3 1.8%<br />
<br />
Leu (L) 21 12.9%<br />
<br />
Lys (K) 6 3.7%<br />
<br />
Met (M) 6 3.7%<br />
<br />
Phe (F) 2 1.2%<br />
<br />
Pro (P) 8 4.9%<br />
<br />
Ser (S) 7 4.3%<br />
<br />
Thr (T) 13 8.0%<br />
<br />
Trp (W) 2 1.2%<br />
<br />
Tyr (Y) 6 3.7%<br />
<br />
Val (V) 12 7.4%<br />
<br />
Pyl (O) 0 0.0%<br />
<br />
Sec (U) 0 0.0%<br />
<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
<br />
<br />
'''Evolution of Irr/Fur'''<br />
<br />
Go to top 5 on Rasmol, put in amino acid sequence and find domain conservations, anything related to Irr/Fur in the past (conserf). Amino acid conservation scores tell you what aa are found in positions in related aa.<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
Go to polyview 3d, select "secondary structures" for coloring mode and re-upload<br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948749User:Adam Meade/Sandbox 12009-04-20T15:19:51Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Function of Irr'''<br />
<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Chemical and Physical Properties of Irr'''<br />
<br />
***Make into a table***<br />
<br />
Amino Acid Composition:<br />
<br />
Ala (A) 15 9.2%<br />
<br />
Arg (R) 10 6.1%<br />
<br />
Asn (N) 6 3.7%<br />
<br />
Asp (D) 10 6.1%<br />
<br />
Cys (C) 1 0.6%<br />
<br />
Gln (Q) 5 3.1%<br />
<br />
Glu (E) 11 6.7%<br />
<br />
Gly (G) 9 5.5%<br />
<br />
His (H) 10 6.1%<br />
<br />
Ile (I) 3 1.8%<br />
<br />
Leu (L) 21 12.9%<br />
<br />
Lys (K) 6 3.7%<br />
<br />
Met (M) 6 3.7%<br />
<br />
Phe (F) 2 1.2%<br />
<br />
Pro (P) 8 4.9%<br />
<br />
Ser (S) 7 4.3%<br />
<br />
Thr (T) 13 8.0%<br />
<br />
Trp (W) 2 1.2%<br />
<br />
Tyr (Y) 6 3.7%<br />
<br />
Val (V) 12 7.4%<br />
<br />
Pyl (O) 0 0.0%<br />
<br />
Sec (U) 0 0.0%<br />
<br />
<br />
Molecular weight: 18338.8 Da<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
<br />
<br />
'''Evolution of Irr/Fur'''<br />
<br />
Go to top 5 on Rasmol, put in amino acid sequence and find domain conservations, anything related to Irr/Fur in the past (conserf)<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
Go to polyview 3d, select "secondary structures" for coloring mode and re-upload<br />
<br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948747User:Adam Meade/Sandbox 12009-04-20T15:05:56Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Function of Irr'''<br />
<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Properties of Irr'''<br />
<br />
Molecular weight: 18338.8<br />
<br />
Theoretical pI: 6.03<br />
<br />
<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
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<br />
<br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948746User:Adam Meade/Sandbox 12009-04-20T15:00:31Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Function of Irr'''<br />
<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='right' caption='3D Image of proposed Irr protein'/><br />
<br />
The amino acid sequence used to derive the structure shown is as follows:<br />
<br />
<br />
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg<br />
<br />
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy<br />
<br />
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr<br />
<br />
<br />
<br />
<br />
<br />
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<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948129User:Adam Meade/Sandbox 12009-04-18T22:05:44Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
'''Function of Irr'''<br />
<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='left' caption='3D Image of proposed Irr protein'/><br />
<br />
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<br />
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<br />
<br />
<br />
<br />
----<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948128User:Adam Meade/Sandbox 12009-04-18T22:05:06Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
'''Function of Irr'''<br />
<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Structure of the Proposed Irr Protein'''<applet load='Irr.pdb' size='300' color='black' frame='true' align='left' caption='3D Image of proposed Irr protein'/><br />
<br />
<br />
<br />
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<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
----<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948126User:Adam Meade/Sandbox 12009-04-18T21:58:22Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
'''Function of Irr'''<br />
<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
'''Structure of the Proposed Irr Protein'''<br />
<applet load='Irr' size='300' color='white' frame='true' align='right' caption='3D Image of proposed Irr protein' /><br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=File:Irr.pdb&diff=948122File:Irr.pdb2009-04-18T21:53:22Z<p>Adam Meade: Proposed 3D structure of Irr protein</p>
<hr />
<div>Proposed 3D structure of Irr protein</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948121User:Adam Meade/Sandbox 12009-04-18T21:42:12Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order ''fecI-fecR-fecABCDE'', encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
'''Function of Irr'''<br />
<br />
Irr behaves differently than other regulatory proteins. It functions as coordinating the heme biosynthetic pathway, which ends with the insertion of Fe<sup>2+</sup> into a protoporphyrin ring to produce protoheme. It also controls the pathway by monitoring iron availability to prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
<br />
<br />
<br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948116User:Adam Meade/Sandbox 12009-04-18T21:34:28Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order fecI-fecR-fecABCDE, encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', ''fecI'' transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, ''fecI'' transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
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==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
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2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948115User:Adam Meade/Sandbox 12009-04-18T21:33:21Z<p>Adam Meade: </p>
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<div>'''''Iron Response Regulator (Irr)'''''<br />
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'''Background Information'''<br />
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Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order fecI-fecR-fecABCDE, encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', fecI transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, fecI transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
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'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
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==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
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2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948114User:Adam Meade/Sandbox 12009-04-18T21:32:30Z<p>Adam Meade: </p>
<hr />
<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order fecI-fecR-fecABCDE, encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', fecI transcription is regulated by Fur in response to iron availability; in ''Bradyrhizobium japonicum'', as well as ''R. sphaeroides'', which both lack Fur, fecI transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein. <ref>1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.</ref><br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell <ref>2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</ref><br />
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==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade/Sandbox_1&diff=948110User:Adam Meade/Sandbox 12009-04-18T21:26:37Z<p>Adam Meade: New page: '''''Iron Response Regulator (Irr)''''' ---- '''Background Information''' Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen sp...</p>
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<div>'''''Iron Response Regulator (Irr)'''''<br />
----<br />
'''Background Information'''<br />
<br />
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in ''Rhodobacter sphaeroides'' form a cluster in the order fecI-fecR-fecABCDE, encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In ''Escherichia coli'', fecI transcription is regulated by Fur in response to iron availability; in ''R. sphaeroides'', which lacks Fur, fecI transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein.<br />
<br />
<br />
<br />
'''Irr and Other Iron-Regulating Proteins'''<br />
<br />
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of ''B. japonicum'', which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
==References==<br />
1) Hamza I, S. Chauhan, R. Hassett, MR O'Brian, 1998. <u>The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.</u>. Journal of Biological Chemistry 34:21669-74.<br />
<br />
2) Small, S. K., S. Puri, and M. R. O’Brian. 2009. <u>Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria</u>. Biometals 22:89-97.</div>Adam Meadehttps://proteopedia.org/index.php?title=User:Adam_Meade&diff=948096User:Adam Meade2009-04-18T20:59:25Z<p>Adam Meade: </p>
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<div>Teaching assistant/researcher, Bowling Green State University<br />
Research interests: iron-response regulators, such as the family of Fec/Fur proteins, and Irr<br />
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*[[User:Adam Meade/Sandbox 1]]</div>Adam Meade