8ssl
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Isobutyryl-CoA mutase fused Q341A in the presence of GTP== | |
| + | <StructureSection load='8ssl' size='340' side='right'caption='[[8ssl]], [[Resolution|resolution]] 4.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8ssl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Cupriavidus_metallidurans_CH34 Cupriavidus metallidurans CH34]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SSL FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.6Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ssl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ssl OCA], [https://pdbe.org/8ssl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ssl RCSB], [https://www.ebi.ac.uk/pdbsum/8ssl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ssl ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ICMF_CUPMC ICMF_CUPMC] Catalyzes the reversible interconversion of isobutyryl-CoA and n-butyryl-CoA, and to a much lesser extent, of pivalyl-CoA and isovaleryl-CoA, using radical chemistry (PubMed:22167181). Also exhibits GTPase activity, associated with its G-protein domain (MeaI) that functions as a chaperone that assists cofactor delivery and proper holo-enzyme assembly (PubMed:22167181, PubMed:25675500). The G-domain of IcmF has also a role in its cofactor repair (PubMed:28130442). Does not display ATPase activity.<ref>PMID:22167181</ref> <ref>PMID:25675500</ref> <ref>PMID:28130442</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | G-protein metallochaperones are essential for the proper maturation of numerous metalloenzymes. The G-protein chaperone MMAA in humans (MeaB in bacteria) uses GTP hydrolysis to facilitate the delivery of adenosylcobalamin (AdoCbl) to AdoCbl-dependent methylmalonyl-CoA mutase, an essential metabolic enzyme. This G-protein chaperone also facilitates the removal of damaged cobalamin (Cbl) for repair. Although most chaperones are standalone proteins, isobutyryl-CoA mutase fused (IcmF) has a G-protein domain covalently attached to its target mutase. We previously showed that dimeric MeaB undergoes a 180 degrees rotation to reach a state capable of GTP hydrolysis (an active G-protein state), in which so-called switch III residues of one protomer contact the G-nucleotide of the other protomer. However, it was unclear whether other G-protein chaperones also adopted this conformation. Here, we show that the G-protein domain in a fused system forms a similar active conformation, requiring IcmF oligomerization. IcmF oligomerizes both upon Cbl damage and in the presence of the nonhydrolyzable GTP analog, guanosine-5'-[(beta,gamma)-methyleno]triphosphate, forming supramolecular complexes observable by mass photometry and EM. Cryo-EM structural analysis reveals that the second protomer of the G-protein intermolecular dimer props open the mutase active site using residues of switch III as a wedge, allowing for AdoCbl insertion or damaged Cbl removal. With the series of structural snapshots now available, we now describe here the molecular basis of G-protein-assisted AdoCbl-dependent mutase maturation, explaining how GTP binding prepares a mutase for cofactor delivery and how GTP hydrolysis allows the mutase to capture the cofactor. | ||
| - | + | Structural insight into G-protein chaperone-mediated maturation of a bacterial adenosylcobalamin-dependent mutase.,Vaccaro FA, Faber DA, Andree GA, Born DA, Kang G, Fonseca DR, Jost M, Drennan CL J Biol Chem. 2023 Sep;299(9):105109. doi: 10.1016/j.jbc.2023.105109. Epub 2023 , Jul 28. PMID:37517695<ref>PMID:37517695</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Drennan | + | <div class="pdbe-citations 8ssl" style="background-color:#fffaf0;"></div> |
| - | [[Category: Vaccaro | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Cupriavidus metallidurans CH34]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Drennan CL]] | ||
| + | [[Category: Vaccaro FA]] | ||
Current revision
Isobutyryl-CoA mutase fused Q341A in the presence of GTP
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