2gci
From Proteopedia
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The 1,1-proton transfer reaction mechanism by alpha-methylacyl-CoA racemase is catalyzed by an asparte/histidine pair and involves a smooth, methionine-rich surface for binding the fatty acyl moiety
Overview
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.
About this Structure
2GCI is a Single protein structure of sequence from Mycobacterium tuberculosis with and as ligands. Active as Alpha-methylacyl-CoA racemase, with EC number 5.1.99.4 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Tue Jan 29 19:56:37 2008
