2GD2

The 1,1-proton transfer reaction mechanism by alpha-methylacyl-CoA racemase is catalyzed by an aspartate/histidine pair and involves a smooth, methionine-rich surface for binding the fatty acyl moiety

Summary for 2GD2

• Entry DOI: 10.2210/pdb2gd2/pdb
• Related: 1X74 2GCE 2GCI 2GD0 2GD6
• Descriptor: probable alpha-methylacyl-CoA racemase MCR, ACETOACETYL-COENZYME A, GLYCEROL, ... (4 entities in total)
• Functional Keywords: alpha-methylacyl-coa racemase, racemase, coa transferase, proton transfer, coenzyme a, isomerase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 4
• Total formula weight: 158481.82

Authors

Bhaumik, P.,Wierenga, R.K. (deposition date: 2006-03-15, release date: 2007-02-20, Last modification date: 2024-12-25)

Primary citation

Bhaumik, P.,Schmitz, W.,Hassinen, A.,Hiltunen, J.K.,Conzelmann, E.,Wierenga, R.K.
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., 367:1145-1161, 2007

PubMed Abstract: 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.

PubMed: 17320106
DOI: 10.1016/j.jmb.2007.01.062

Experimental method

X-RAY DIFFRACTION (1.7 Å)