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4r3u

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Crystal structure of 2-Hydroxyisobutyryl-CoA Mutase

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 <StructureSection load='4r3u' size='340' side='right'caption='[[4r3u]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4r3u]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Aquicola_tertiaricarbonis Aquicola tertiaricarbonis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R3U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R3U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4r3u]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquincola_tertiaricarbonis Aquincola tertiaricarbonis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R3U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R3U FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3HC:3-HYDROXYBUTANOYL-COENZYME+A'>3HC</scene>, <scene name='pdbligand=3KK:S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-4-HYDROXY-3-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]-3,5,9-TRIHYDROXY-8,8-DIMETHYL-3,5-DIOXIDO-10,14-DIOXO-2,4,6-TRIOXA-11,15-DIAZA-3LAMBDA~5~,5LAMBDA~5~-DIPHOSPHAHEPTADECAN-17-YL}+2-HYDROXY-2-METHYLPROPANETHIOATE'>3KK</scene>, <scene name='pdbligand=5AD:5-DEOXYADENOSINE'>5AD</scene>, <scene name='pdbligand=B12:COBALAMIN'>B12</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4req|4req]], [[2xiq|2xiq]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3HC:3-HYDROXYBUTANOYL-COENZYME+A'>3HC</scene>, <scene name='pdbligand=3KK:S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-4-HYDROXY-3-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]-3,5,9-TRIHYDROXY-8,8-DIMETHYL-3,5-DIOXIDO-10,14-DIOXO-2,4,6-TRIOXA-11,15-DIAZA-3LAMBDA~5~,5LAMBDA~5~-DIPHOSPHAHEPTADECAN-17-YL}+2-HYDROXY-2-METHYLPROPANETHIOATE'>3KK</scene>, <scene name='pdbligand=5AD:5-DEOXYADENOSINE'>5AD</scene>, <scene name='pdbligand=B12:COBALAMIN'>B12</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hcmA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=391953 Aquicola tertiaricarbonis]), hcmB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=391953 Aquicola tertiaricarbonis])</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=4r3u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r3u OCA], [https://pdbe.org/4r3u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r3u RCSB], [https://www.ebi.ac.uk/pdbsum/4r3u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r3u ProSAT]</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=4r3u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r3u OCA], [http://pdbe.org/4r3u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r3u RCSB], [http://www.ebi.ac.uk/pdbsum/4r3u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r3u ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/HCMA_AQUTE HCMA_AQUTE] Together with HcmB, catalyzes the isomerization of 2-hydroxyisobutyryl-CoA and 3-hydroxybutyryl-CoA. Is specific for 2-hydroxyisobutyryl-CoA and (S)-3-hydroxybutyryl-CoA, and shows only very low activity with (R)-3-hydroxybutyryl-CoA, isobutyryl-CoA and butyryl-CoA (PubMed:22433853, PubMed:25720495). In vitro, can isomerize pivalyl-CoA and isovaleryl-CoA, with much lower efficiency (PubMed:25720495). Plays a central role in the degradation of substrates bearing a tert-butyl moiety, such as the fuel oxygenate methyl tert-butyl ether (MTBE) and its metabolites (PubMed:22433853).<ref>PMID:22433853</ref> <ref>PMID:25720495</ref>
-Bacterial coenzyme B12-dependent 2-hydroxyisobutyryl-CoA mutase (HCM) is a radical enzyme catalyzing the stereospecific interconversion of (S)-3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA. It consists of two subunits, HcmA and HcmB. To characterize the determinants of substrate specificity, we have analyzed the crystal structure of HCM from Aquincola tertiaricarbonis in complex with coenzyme B12 and the substrates (S)-3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA in alternative binding. When compared with the well studied structure of bacterial and mitochondrial B12-dependent methylmalonyl-CoA mutase (MCM), HCM has a highly conserved domain architecture. However, inspection of the substrate binding site identified amino acid residues not present in MCM, namely HcmA Ile(A90) and Asp(A117). Asp(A117) determines the orientation of the hydroxyl group of the acyl-CoA esters by H-bond formation, thus determining stereospecificity of catalysis. Accordingly, HcmA D117A and D117V mutations resulted in significantly increased activity toward (R)-3-hydroxybutyryl-CoA. Besides interconversion of hydroxylated acyl-CoA esters, wild-type HCM as well as HcmA I90V and I90A mutant enzymes could also isomerize pivalyl- and isovaleryl-CoA, albeit at &gt;10 times lower rates than the favorite substrate (S)-3-hydroxybutyryl-CoA. The nonconservative mutation HcmA D117V, however, resulted in an enzyme showing high activity toward pivalyl-CoA. Structural requirements for binding and isomerization of highly branched acyl-CoA substrates such as 2-hydroxyisobutyryl- and pivalyl-CoA, possessing tertiary and quaternary carbon atoms, respectively, are discussed.
-Structural basis of the stereospecificity of bacterial B12-dependent 2-hydroxyisobutyryl-CoA mutase.,Kurteva-Yaneva N, Zahn M, Weichler MT, Starke R, Harms H, Muller RH, Strater N, Rohwerder T J Biol Chem. 2015 Apr 10;290(15):9727-37. doi: 10.1074/jbc.M115.645689. Epub 2015, Feb 26. PMID:25720495<ref>PMID:25720495</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4r3u" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Aquicola tertiaricarbonis]]
+[[Category: Aquincola tertiaricarbonis]]
 [[Category: Large Structures]]
-[[Category: Kurteva-Yaneva, N]]
+[[Category: Kurteva-Yaneva N]]
-[[Category: Rohwerder, T]]
+[[Category: Rohwerder T]]
-[[Category: Straeter, N]]
+[[Category: Straeter N]]
-[[Category: Zahn, M]]
+[[Category: Zahn M]]
-[[Category: Coa]]
-[[Category: Isomerase]]
-[[Category: Mutase]]
-[[Category: Tim rossmann fold]]

4r3u

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Crystal structure of 2-Hydroxyisobutyryl-CoA Mutase

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