Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha-Methylacyl-CoA racemase is a key enzyme in the metabolism of 2-methyl-branched fatty acids and, in mammals, in the conversion of cholesterol to bile acids. The enzyme from Mycobacterium tuberculosis has been purified to homogeneity and crystallized by the hanging-drop vapour-diffusion method. The crystals of the unliganded racemase belong to space group P6(1)22 or P6(5)22, with unit-cell parameters a = b = 122.0, c = 256.4 A. Data sets were collected at 100 K. The crystals diffract to 2.8 A using synchrotron radiation.
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PMID:Crystallization and preliminary X-ray diffraction studies of an alpha-methylacyl-CoA racemase from Mycobacterium tuberculosis. 1255 51

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.
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PMID: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. 1732 Jan 6