title: A structural basis for enantioselective inhibition of Candida rugosa lipase by long-chain aliphatic alcohols.
abstract: Molecular modeling showed that the enantiomers of heptyl 2-methyldecanoate are productively bound to the active site of Candida rugosa lipase in quite different conformations. The fast-reacting S-enantiomer may well occupy the previously identified acyl-binding tunnel in the active site of the lipase. By contrast, the slow-reacting R-enantiomer must be bound to the active site, leaving the tunnel empty to allow the formation of two catalytically essential hydrogen bonds between His 449 of the catalytic triad and the transition state of the catalyzed reaction. This information enables us to propose a molecular mechanism explaining how long-chain aliphatic alcohols act as enantioselective inhibitors of this lipase in the resolution of 2-methyldecanoic acid. Long-chain aliphatic alcohols may coordinate to the acyl-binding tunnel of the C. rugosa lipase, thereby selectively inhibiting the turnover of the fast-reacting S-enantiomer, thus resulting in a lowered enantioselectivity in the resolution.
authors.affiliation: Department of Biochemistry and Biotechnology, Royal Institute of Technology, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Holmquist
authors.forename: F
authors.initials: F
authors.lastname: Haeffner
authors.forename: T
authors.initials: T
authors.lastname: Norin
authors.forename: K
authors.initials: K
authors.lastname: Hult
mesh_terms: D000438:Alcohols / Q000494:pharmacology*; D002175:Candida / Q000201:enzymology*; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000438:Alcohols; D004791:Enzyme Inhibitors; D008049:Lipase