Switched enantiopreference of Humicola lipase for 2-phenoxyalkanoic acid ester homologs can be rationalized by different substrate binding modes
1999; Elsevier BV; Volume: 10; Issue: 21 Linguagem: Inglês
10.1016/s0957-4166(99)00438-3
ISSN1362-511X
AutoresPer Berglund, Imre Vallikivi, Linda Fransson, Heinz Dannacher, Mats Holmquist, Mats Martinelle, Fredrik Björkling, Omar Parve, Karl Hult,
Tópico(s)Pharmacogenetics and Drug Metabolism
ResumoHumicola lanuginosa lipase was used for enantioselective hydrolyses of a series of homologous 2-phenoxyalkanoic acid ethyl esters. The enantioselectivity (E-value) of the enzyme changed from an (R)-enantiomer preference for the smallest substrate, 2-phenoxypropanoic acid ester, to an (S)-enantiomer preference for the homologous esters with longer acyl moieties. The E-values span the range from E=13 (R) to E=56 (S). A molecular modeling study identified two different substrate-binding modes for each enantiomer. We found that the enantiomers favored different modes. This discovery provided a model that offered a rational explanation for the observed switch in enantioselectivity.
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