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| | <StructureSection load='5cjt' size='340' side='right'caption='[[5cjt]], [[Resolution|resolution]] 3.40Å' scene=''> | | <StructureSection load='5cjt' size='340' side='right'caption='[[5cjt]], [[Resolution|resolution]] 3.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5cjt]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cupmc Cupmc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CJT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CJT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5cjt]] is a 2 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=5CJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CJT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5AD:5-DEOXYADENOSINE'>5AD</scene>, <scene name='pdbligand=B12:COBALAMIN'>B12</scene>, <scene name='pdbligand=CO6:ISOBUTYRYL-COENZYME+A'>CO6</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5AD:5-DEOXYADENOSINE'>5AD</scene>, <scene name='pdbligand=B12:COBALAMIN'>B12</scene>, <scene name='pdbligand=CO6:ISOBUTYRYL-COENZYME+A'>CO6</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xc6|4xc6]], [[4xc7|4xc7]], [[4xc8|4xc8]], [[5cju|5cju]], [[5cjv|5cjv]], [[5cjw|5cjw]]</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=5cjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cjt OCA], [https://pdbe.org/5cjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cjt RCSB], [https://www.ebi.ac.uk/pdbsum/5cjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cjt ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">sbm, Rmet_0210 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=266264 CUPMC])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methylmalonyl-CoA_mutase Methylmalonyl-CoA mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.2 5.4.99.2] </span></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=5cjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cjt OCA], [http://pdbe.org/5cjt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cjt RCSB], [http://www.ebi.ac.uk/pdbsum/5cjt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cjt ProSAT]</span></td></tr> | + | |
| | </table> | | </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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cupmc]] | + | [[Category: Cupriavidus metallidurans CH34]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Methylmalonyl-CoA mutase]]
| + | [[Category: Drennan CL]] |
| - | [[Category: Drennan, C L]] | + | [[Category: Jost M]] |
| - | [[Category: Jost, M]] | + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: G-protein chaperone]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Radical enzyme]]
| + | |
| Structural highlights
Function
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.[1] [2] [3]
Publication Abstract from PubMed
Acyl-CoA mutases are a growing class of adenosylcobalamin-dependent radical enzymes that perform challenging carbon skeleton rearrangements in primary and secondary metabolism. Members of this class of enzymes must precisely control substrate positioning to prevent oxidative interception of radical intermediates during catalysis. Our understanding of substrate specificity and catalysis in acyl-CoA mutases, however, is incomplete. Here, we present crystal structures of IcmF, a natural fusion protein variant of isobutyryl-CoA mutase, in complex with the adenosylcobalamin cofactor and four different acyl-CoA substrates. These structures demonstrate how the active site is designed to accommodate the aliphatic acyl chains of each substrate. The structures suggest that a conformational change of the 5'-deoxyadenosyl group from C2'-endo to C3'-endo could contribute to initiation of catalysis. Furthermore, detailed bioinformatic analyses guided by our structural findings identify critical determinants of acyl-CoA mutase substrate specificity and predict new acyl-CoA mutase-catalyzed reactions. These results expand our understanding of substrate specificity and catalytic scope of acyl-CoA mutases and could benefit engineering efforts for biotechnological applications ranging from production of biofuels and commercial products to hydrocarbon remediation.
Structural Basis for Substrate Specificity in Adenosylcobalamin-Dependent Isobutyryl-CoA Mutase and Related Acyl-CoA Mutases.,Jost M, Born DA, Cracan V, Banerjee R, Drennan CL J Biol Chem. 2015 Aug 28. pii: jbc.M115.676890. PMID:26318610[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cracan V, Banerjee R. Novel coenzyme B12-dependent interconversion of isovaleryl-CoA and pivalyl-CoA. J Biol Chem. 2012 Feb 3;287(6):3723-32. PMID:22167181 doi:10.1074/jbc.M111.320051
- ↑ Jost M, Cracan V, Hubbard PA, Banerjee R, Drennan CL. Visualization of a radical B12 enzyme with its G-protein chaperone. Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2419-24. doi:, 10.1073/pnas.1419582112. Epub 2015 Feb 9. PMID:25675500 doi:http://dx.doi.org/10.1073/pnas.1419582112
- ↑ Li Z, Kitanishi K, Twahir UT, Cracan V, Chapman D, Warncke K, Banerjee R. Cofactor Editing by the G-protein Metallochaperone Domain Regulates the Radical B(12) Enzyme IcmF. J Biol Chem. 2017 Mar 10;292(10):3977-3987. PMID:28130442 doi:10.1074/jbc.M117.775957
- ↑ Jost M, Born DA, Cracan V, Banerjee R, Drennan CL. Structural Basis for Substrate Specificity in Adenosylcobalamin-Dependent Isobutyryl-CoA Mutase and Related Acyl-CoA Mutases. J Biol Chem. 2015 Aug 28. pii: jbc.M115.676890. PMID:26318610 doi:http://dx.doi.org/10.1074/jbc.M115.676890
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