Back to Search
Start Over
The Catalysis of the 1,1-Proton Transfer by α-Methyl-acyl-CoA Racemase Is Coupled to a Movement of the Fatty Acyl Moiety Over a Hydrophobic, Methionine-rich Surface
- Source :
-
Journal of Molecular Biology . Apr2007, Vol. 367 Issue 4, p1145-1161. 17p. - Publication Year :
- 2007
-
Abstract
- Abstract: α-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 α-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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00222836
- Volume :
- 367
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 24381776
- Full Text :
- https://doi.org/10.1016/j.jmb.2007.01.062