2q6o: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
(14 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2q6o.jpg|left|200px]]<br /><applet load="2q6o" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2q6o, resolution 2.00&Aring;" />
'''SalL-Y70T with SAM and Cl'''<br />


==Overview==
==SalL-Y70T with SAM and Cl==
Halogen atom incorporation into a scaffold of bioactive compounds often amplifies biological activity, as is the case for the anticancer agent salinosporamide A (1), a chlorinated natural product from the marine bacterium Salinispora tropica. Significant effort in understanding enzymatic chlorination shows that oxidative routes predominate to form reactive electrophilic or radical chlorine species. Here we report the genetic, biochemical and structural characterization of the chlorinase SalL, which halogenates S-adenosyl-L-methionine (2) with chloride to generate 5'-chloro-5'-deoxyadenosine (3) and L-methionine (4) in a rarely observed nucleophilic substitution strategy analogous to that of Streptomyces cattleya fluorinase. Further metabolic tailoring produces a halogenated polyketide synthase substrate specific for salinosporamide A biosynthesis. SalL also accepts bromide and iodide as substrates, but not fluoride. High-resolution crystal structures of SalL and active site mutants complexed with substrates and products support the S(N)2 nucleophilic substitution mechanism and further illuminate halide specificity in this newly discovered halogenase family.
<StructureSection load='2q6o' size='340' side='right'caption='[[2q6o]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[2q6o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Salinispora_tropica_CNB-440 Salinispora tropica CNB-440]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q6O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q6O FirstGlance]. <br>
2Q6O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacteria Bacteria] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=SAM:'>SAM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q6O OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2q6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q6o OCA], [https://pdbe.org/2q6o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q6o RCSB], [https://www.ebi.ac.uk/pdbsum/2q6o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q6o ProSAT]</span></td></tr>
Discovery and characterization of a marine bacterial SAM-dependent chlorinase., Eustaquio AS, Pojer F, Noel JP, Moore BS, Nat Chem Biol. 2008 Jan;4(1):69-74. Epub 2007 Dec 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18059261 18059261]
</table>
[[Category: Bacteria]]
== Function ==
[[Category: Single protein]]
[https://www.uniprot.org/uniprot/SALL_SALTO SALL_SALTO] Involved in the biosynthesis of the proteosome inhibitor salinosporamide A (SalA). Catalyzes the halogenation of S-adenosyl-L-methionine (SAM) with chloride to generate 5'-chloro-5'-deoxyadenosine (5'-CIDA) and L-methionine. It can also use bromide and iodide, producing halogenated 5'-deoxyadenosine (5'-XDA) and L-methionine, however no halogenase activity is detected in the presence of fluoride.<ref>PMID:18059261</ref>
[[Category: Noel, J P.]]
== Evolutionary Conservation ==
[[Category: Pojer, F.]]
[[Image:Consurf_key_small.gif|200px|right]]
[[Category: CL]]
Check<jmol>
[[Category: SAM]]
  <jmolCheckbox>
[[Category: biosynthetic protein]]
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q6/2q6o_consurf.spt"</scriptWhenChecked>
[[Category: chlorinase]]
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
[[Category: y70t mutant sam and cl complex]]
    <text>to colour the structure by Evolutionary Conservation</text>
 
  </jmolCheckbox>
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:36:33 2008''
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2q6o ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Salinispora tropica CNB-440]]
[[Category: Noel JP]]
[[Category: Pojer F]]
Retrieved from "https://proteopedia.org/2q6o"