4lc1: Difference between revisions

Line 1:

~~{{STRUCTURE_4lc1| PDB=4lc1 | SCENE= }}~~

==MeaB, A Bacterial Homolog of MMAA, Bound to GDP and crystallized in the presence of GDP and [AlF4]-==

===MeaB, A Bacterial Homolog of MMAA, Bound to GDP and crystallized in the presence of GDP and [AlF4]-===

~~{{ABSTRACT_PUBMED_23996001}}~~

== Structural highlights ==

<table><tr><td colspan='2'>[[4lc1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Metea Metea]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LC1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LC1 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">meaB, MexAM1_META1p0188 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272630 METEA])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lc1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lc1 RCSB], [http://www.ebi.ac.uk/pdbsum/4lc1 PDBsum]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

MeaB is an accessory GTPase protein involved in the assembly, protection and reactivation of 5'-deoxyadenosylcobalamin-dependent methyl malonyl-CoA mutase (MCM). Mutations in the human ortholog of MeaB result in methylmalonic aciduria, an inborn error of metabolism. G-proteins typically utilize conserved switch I and II motifs for signaling to effector proteins via conformational changes elicited by nucleotide-binding and hydrolysis. Our recent discovery that MeaB employs an unusual switch III region for bidirectional signaling with MCM raised questions about the roles of the switch I and II motifs in MeaB. In this study, we have addressed the functions of conserved switch II residues by performing alanine-scanning mutagenesis. Our results demonstrate that the GTPase activity of MeaB is auto-inhibited by switch II and that this loop is important for coupling nucleotide-sensitive conformational changes in switch III to elicit the multiple chaperone functions of MeaB. Furthermore, we report the structure of MeaB-GDP crystallized in the presence of AlFx- in order to form the putative transition state analog, GDP-AlF4-. The resulting crystal structure and its comparison to related G-proteins supports the conclusion that the catalytic site of MeaB is incomplete in the absence of the GTPase-activating protein, MCM, and therefore unable to stabilize the transition state analog. Favoring an inactive conformation in the absence of the client MCM protein might represent a strategy for suppressing the intrinsic GTPase activity of MeaB in which the switch II loop plays an important role.

~~==About this Structure==~~

Autoinhibition and signalling by the switch II motif in the G-protein chaperone of a radical B12 enzyme.,Lofgren M, Koutmos M, Banerjee R J Biol Chem. 2013 Aug 30. PMID:23996001<ref>PMID:23996001</ref>

~~[[4lc1]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Metea Metea]~~. ~~Full crystallographic information is available from [http~~:/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4LC1 OCA].~~

==~~Reference~~==

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

~~<ref group="xtra">PMID:023996001</ref>~~<references ~~group="xtra"~~/><~~references~~/>

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Metea]]

[[Category: Banerjee, R.]]

[[Category: Banerjee, R]]

[[Category: Koutmos, M.]]

[[Category: Koutmos, M]]

[[Category: Lofgren, M.]]

[[Category: Lofgren, M]]

[[Category: Padovani, D.]]

[[Category: Padovani, D]]

[[Category: Alpha and beta protein]]

[[Category: Chaperone]]

[[Category: Metallochaperone]]

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@@ Line 1: / Line 1: @@
-{{STRUCTURE_4lc1|  PDB=4lc1  |  SCENE=  }}
+==MeaB, A Bacterial Homolog of MMAA, Bound to GDP and crystallized in the presence of GDP and [AlF4]-==
-===MeaB, A Bacterial Homolog of MMAA, Bound to GDP and crystallized in the presence of GDP and [AlF4]-===
+<StructureSection load='4lc1' size='340' side='right' caption='[[4lc1]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
-{{ABSTRACT_PUBMED_23996001}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4lc1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Metea Metea]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LC1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LC1 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jyb|4jyb]], [[4jyc|4jyc]], [[2qm7|2qm7]], [[2qm8|2qm8]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">meaB, MexAM1_META1p0188 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272630 METEA])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lc1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lc1 RCSB], [http://www.ebi.ac.uk/pdbsum/4lc1 PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+MeaB is an accessory GTPase protein involved in the assembly, protection and reactivation of 5'-deoxyadenosylcobalamin-dependent methyl malonyl-CoA mutase (MCM). Mutations in the human ortholog of MeaB result in methylmalonic aciduria, an inborn error of metabolism. G-proteins typically utilize conserved switch I and II motifs for signaling to effector proteins via conformational changes elicited by nucleotide-binding and hydrolysis. Our recent discovery that MeaB employs an unusual switch III region for bidirectional signaling with MCM raised questions about the roles of the switch I and II motifs in MeaB. In this study, we have addressed the functions of conserved switch II residues by performing alanine-scanning mutagenesis. Our results demonstrate that the GTPase activity of MeaB is auto-inhibited by switch II and that this loop is important for coupling nucleotide-sensitive conformational changes in switch III to elicit the multiple chaperone functions of MeaB. Furthermore, we report the structure of MeaB-GDP crystallized in the presence of AlFx- in order to form the putative transition state analog, GDP-AlF4-. The resulting crystal structure and its comparison to related G-proteins supports the conclusion that the catalytic site of MeaB is incomplete in the absence of the GTPase-activating protein, MCM, and therefore unable to stabilize the transition state analog. Favoring an inactive conformation in the absence of the client MCM protein might represent a strategy for suppressing the intrinsic GTPase activity of MeaB in which the switch II loop plays an important role.
-==About this Structure==
+Autoinhibition and signalling by the switch II motif in the G-protein chaperone of a radical B12 enzyme.,Lofgren M, Koutmos M, Banerjee R J Biol Chem. 2013 Aug 30. PMID:23996001<ref>PMID:23996001</ref>
-[[4lc1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Metea Metea]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LC1 OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<ref group="xtra">PMID:023996001</ref><references group="xtra"/><references/>
+</div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Metea]]
-[[Category: Banerjee, R.]]
+[[Category: Banerjee, R]]
-[[Category: Koutmos, M.]]
+[[Category: Koutmos, M]]
-[[Category: Lofgren, M.]]
+[[Category: Lofgren, M]]
-[[Category: Padovani, D.]]
+[[Category: Padovani, D]]
 [[Category: Alpha and beta protein]]
 [[Category: Chaperone]]
 [[Category: Metallochaperone]]