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(4): 1145-61, 2007 Apr 06.
Article
em En
| MEDLINE
| ID: mdl-17320106
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Prótons
/
Acil Coenzima A
/
Racemases e Epimerases
/
Interações Hidrofóbicas e Hidrofílicas
/
Metionina
Idioma:
En
Revista:
J Mol Biol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Finlândia
País de publicação:
Holanda