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| | <StructureSection load='1e1c' size='340' side='right'caption='[[1e1c]], [[Resolution|resolution]] 2.62Å' scene=''> | | <StructureSection load='1e1c' size='340' side='right'caption='[[1e1c]], [[Resolution|resolution]] 2.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1e1c]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E1C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1e1c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Propionibacterium_freudenreichii_subsp._shermanii Propionibacterium freudenreichii subsp. shermanii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E1C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B12:COBALAMIN'>B12</scene>, <scene name='pdbligand=DCA:DESULFO-COENZYME+A'>DCA</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]] 2.62Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1req|1req]], [[2req|2req]], [[3req|3req]], [[4req|4req]], [[5req|5req]], [[6req|6req]], [[7req|7req]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B12:COBALAMIN'>B12</scene>, <scene name='pdbligand=DCA:DESULFO-COENZYME+A'>DCA</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methylmalonyl-CoA_mutase Methylmalonyl-CoA mutase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=1e1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e1c OCA], [https://pdbe.org/1e1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e1c RCSB], [https://www.ebi.ac.uk/pdbsum/1e1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e1c ProSAT]</span></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=1e1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e1c OCA], [https://pdbe.org/1e1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e1c RCSB], [https://www.ebi.ac.uk/pdbsum/1e1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e1c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MUTB_PROFR MUTB_PROFR]] Catalyzes the isomerization of succinyl-CoA to methylmalonyl-CoA during synthesis of propionate from tricarboxylic acid-cycle intermediates. [[https://www.uniprot.org/uniprot/MUTA_PROFR MUTA_PROFR]] Catalyzes the isomerization of succinyl-CoA to methylmalonyl-CoA during synthesis of propionate from tricarboxylic acid-cycle intermediates.
| + | [https://www.uniprot.org/uniprot/MUTB_PROFR MUTB_PROFR] Catalyzes the isomerization of succinyl-CoA to methylmalonyl-CoA during synthesis of propionate from tricarboxylic acid-cycle intermediates. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Methylmalonyl-CoA mutase]] | + | [[Category: Propionibacterium freudenreichii subsp. shermanii]] |
| - | [[Category: Evans, P R]] | + | [[Category: Evans PR]] |
| - | [[Category: Thoma, N H]] | + | [[Category: Thoma NH]] |
| - | [[Category: Intramolecular transferase]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Mutase]]
| + | |
| Structural highlights
Function
MUTB_PROFR Catalyzes the isomerization of succinyl-CoA to methylmalonyl-CoA during synthesis of propionate from tricarboxylic acid-cycle intermediates.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Adenosylcobalamin-dependent methylmalonyl-CoA mutase catalyzes the interconversion of methylmalonyl-CoA and succinyl-CoA via radical intermediates generated by substrate-induced homolysis of the coenzyme carbon-cobalt bond. From the structure of methylmalonyl-CoA mutase it is evident that the deeply buried active site is completely shielded from solvent with only a few polar contacts made between the protein and the substrate. Site-directed mutants of amino acid His244, a residue close to the inferred site of radical chemistry, were engineered to investigate its role in catalysis. Two mutants, His244Ala and His244Gln, were characterized using kinetic and spectroscopic techniques. These results confirmed that His244 is not an essential residue. However, compared with that of the wild type, k(cat) was lowered by 10(2)- and 10(3)-fold for the His244Gln and His244Ala mutants, respectively, while the K(m) for succinyl-CoA was essentially unchanged in both cases. The primary kinetic tritium isotope effect (k(H)/k(T)) for the His244Gln mutant was 1.5 +/- 0.3, and tritium partitioning was now found to be dependent on the substrate used to initiate the reaction, indicating that the rearrangement of the substrate radical to the product radical was extremely slow. The His244Ala mutant underwent inactivation under aerobic conditions at a rate between 1 and 10% of the initial rate of turnover. The crystal structure of the His244Ala mutant, determined at 2.6 A resolution, indicated that the mutant enzyme is unaltered except for a cavity in the active site which is occupied by an ordered water molecule. Molecular oxygen reaching this cavity may lead directly to inactivation. These results indicate that His244 assists directly in the unusual carbon skeleton rearrangement and that alterations in this residue substantially lower the protection of reactive radical intermediates during catalysis.
Protection of radical intermediates at the active site of adenosylcobalamin-dependent methylmalonyl-CoA mutase.,Thoma NH, Evans PR, Leadlay PF Biochemistry. 2000 Aug 8;39(31):9213-21. PMID:10924114[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Thoma NH, Evans PR, Leadlay PF. Protection of radical intermediates at the active site of adenosylcobalamin-dependent methylmalonyl-CoA mutase. Biochemistry. 2000 Aug 8;39(31):9213-21. PMID:10924114
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