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| | <StructureSection load='2gce' size='340' side='right'caption='[[2gce]], [[Resolution|resolution]] 1.85Å' scene=''> | | <StructureSection load='2gce' size='340' side='right'caption='[[2gce]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2gce]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GCE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2gce]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GCE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RFC:(R)-IBUPROFENOYL-COENZYME+A'>RFC</scene>, <scene name='pdbligand=SFC:(S)-IBUPROFENOYL-COENZYME+A'>SFC</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]] 1.85Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1x74|1x74]], [[2gci|2gci]], [[2gd0|2gd0]], [[2gd2|2gd2]], [[2gd6|2gd6]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RFC:(R)-IBUPROFENOYL-COENZYME+A'>RFC</scene>, <scene name='pdbligand=SFC:(S)-IBUPROFENOYL-COENZYME+A'>SFC</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CAB09031 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Alpha-methylacyl-CoA_racemase Alpha-methylacyl-CoA racemase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.99.4 5.1.99.4] </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=2gce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gce OCA], [https://pdbe.org/2gce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gce RCSB], [https://www.ebi.ac.uk/pdbsum/2gce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gce 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=2gce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gce OCA], [https://pdbe.org/2gce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gce RCSB], [https://www.ebi.ac.uk/pdbsum/2gce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gce ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/AMACR_MYCTU AMACR_MYCTU] Catalyzes the epimerization of (2R)- and (2S)-methylacyl-coenzyme A (CoA) thioesters (PubMed:15632186, PubMed:19854148, PubMed:26348625). Accepts as substrates a wide range of alpha-methylacyl-CoAs, including (2R)-2-methylmyristoyl-CoA and (2S)-2-methylmyristoyl-CoA, (2R)-pristanoyl-CoA and (2S)-pristanoyl-CoA, and the cholesterol esters (25R)-3-oxo-cholest-4-en-26-oyl-CoA and (25S)-3-oxo-cholest-4-en-26-oyl-CoA (PubMed:15632186, PubMed:26348625). Can also catalyze the interconversion of the non-physiologic substrates (2R)-ibuprofenoyl-CoA and (2S)-ibuprofenoyl-CoA, which are potential competitive inhibitors of the enzyme (PubMed:19854148).<ref>PMID:15632186</ref> <ref>PMID:19854148</ref> <ref>PMID:26348625</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alpha-methylacyl-CoA racemase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bhaumik, P]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Wierenga, R K]] | + | [[Category: Bhaumik P]] |
| - | [[Category: Alpha-methylacyl-coa racemase]] | + | [[Category: Wierenga RK]] |
| - | [[Category: Coa transferase]]
| + | |
| - | [[Category: Coenzyme some]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Proton transfer]]
| + | |
| - | [[Category: Racemase]]
| + | |
| Structural highlights
Function
AMACR_MYCTU Catalyzes the epimerization of (2R)- and (2S)-methylacyl-coenzyme A (CoA) thioesters (PubMed:15632186, PubMed:19854148, PubMed:26348625). Accepts as substrates a wide range of alpha-methylacyl-CoAs, including (2R)-2-methylmyristoyl-CoA and (2S)-2-methylmyristoyl-CoA, (2R)-pristanoyl-CoA and (2S)-pristanoyl-CoA, and the cholesterol esters (25R)-3-oxo-cholest-4-en-26-oyl-CoA and (25S)-3-oxo-cholest-4-en-26-oyl-CoA (PubMed:15632186, PubMed:26348625). Can also catalyze the interconversion of the non-physiologic substrates (2R)-ibuprofenoyl-CoA and (2S)-ibuprofenoyl-CoA, which are potential competitive inhibitors of the enzyme (PubMed:19854148).[1] [2] [3]
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
Alpha-methylacyl-CoA racemases are essential enzymes for branched-chain fatty acid metabolism. Their reaction mechanism and the structural basis of their wide substrate specificity are poorly understood. High-resolution crystal structures of Mycobacterium tuberculosis alpha-methylacyl-CoA racemase (MCR) complexed with substrate molecules show the active site geometry required for catalysis of the interconversion of (2S) and (2R)-methylacyl-CoA. The thioester oxygen atom and the 2-methyl group are in a cis-conformation with respect to each other. The thioester oxygen atom fits into an oxyanion hole and the 2-methyl group points into a hydrophobic pocket. The active site geometry agrees with a 1,1-proton transfer mechanism in which the acid/base-pair residues are His126 and Asp156. The structures of the complexes indicate that the acyl chains of the S-substrate and the R-substrate bind in an S-pocket and an R-pocket, respectively. A unique feature of MCR is a large number of methionine residues in the acyl binding region, located between the S-pocket and the R-pocket. It appears that the (S) to (R) interconversion of the 2-methylacyl chiral center is coupled to a movement of the acyl group over this hydrophobic, methionine-rich surface, when moving from its S-pocket to its R-pocket, whereas the 2-methyl moiety and the CoA group remain fixed in their respective pockets.
The catalysis of the 1,1-proton transfer by alpha-methyl-acyl-CoA racemase is coupled to a movement of the fatty acyl moiety over a hydrophobic, methionine-rich surface.,Bhaumik P, Schmitz W, Hassinen A, Hiltunen JK, Conzelmann E, Wierenga RK J Mol Biol. 2007 Apr 6;367(4):1145-61. Epub 2007 Jan 27. PMID:17320106[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Savolainen K, Bhaumik P, Schmitz W, Kotti TJ, Conzelmann E, Wierenga RK, Hiltunen JK. Alpha-methylacyl-CoA racemase from Mycobacterium tuberculosis. Mutational and structural characterization of the active site and the fold. J Biol Chem. 2005 Apr 1;280(13):12611-20. Epub 2005 Jan 4. PMID:15632186 doi:10.1074/jbc.M409704200
- ↑ Ouazia D, Bearne SL. A continuous assay for alpha-methylacyl-coenzyme A racemase using circular dichroism. Anal Biochem. 2010 Mar 1;398(1):45-51. PMID:19854148 doi:10.1016/j.ab.2009.10.039
- ↑ Lu R, Schmitz W, Sampson NS. α-Methyl Acyl CoA Racemase Provides Mycobacterium tuberculosis Catabolic Access to Cholesterol Esters. Biochemistry. 2015 Sep 22;54(37):5669-72. PMID:26348625 doi:10.1021/acs.biochem.5b00911
- ↑ Bhaumik P, Schmitz W, Hassinen A, Hiltunen JK, Conzelmann E, Wierenga RK. The catalysis of the 1,1-proton transfer by alpha-methyl-acyl-CoA racemase is coupled to a movement of the fatty acyl moiety over a hydrophobic, methionine-rich surface. J Mol Biol. 2007 Apr 6;367(4):1145-61. Epub 2007 Jan 27. PMID:17320106 doi:http://dx.doi.org/10.1016/j.jmb.2007.01.062
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