Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/4476
Title: Computer Simulations of Enantioselective Ester Hydrolyses Catalyzed by Pseudomonas cepacia Lipase
Authors: Tafi, Andrea 
Van Almsick, Andreas
Corelli, Federico 
Crusco, Maria
Laumen Kurt, E.
Schneider Manfred, P.
Botta, Maurizio 
Issue Date: 2000
Project: None 
Journal: JOURNAL OF ORGANIC CHEMISTRY
Abstract: 
On the basis of the X-ray crystal structure of the lipase from Pseudomonas cepacia (PcL), an enzyme representative for a whole family of Pseudomonas lipases (lipase PS, SAM-2, AK 10, and others with a high degree of homol. with PcL), a computational study was performed to rationalize both the enantioselectivity and substrate specificity (tolerance) displayed by this lipase in the enantioselective hydrolysis of racemic esters 1a-12a from various secondary arom. alcs. The major goal of this project was the development of a binding model for PcL which is able to rationalize the exptl. findings to predict a priori the enantioselective behavior of PcL toward a wider range of substrates. A two-step modeling procedure, namely, docking expts. followed by construction of tetrahedral intermediates, was used for the simulation of the involved enzyme-substrate recognition/hydrolysis processes. The study of the recognition process (docking expts.) led to unambiguous identification of the binding geometry for the two enantiomeric series of substrates, but did not suggest a definitive interpretation of the behavior of PcL. Taking into consideration the stereoelectronic requirements of the enzymic hydrolysis reaction, both the enantioselectivity and tolerance of the enzyme were then explained through the study of the tetrahedral intermediates, in turn constructed from the calcd. docking geometries of 1a-12a.
Description: 
44549
URI: http://hdl.handle.net/20.500.12779/4476
ISSN: 0022-3263
DOI: 10.1021/jo9919198
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