title: Probing the substrate specificity for lipases. II. Kinetic and modeling studies on the molecular recognition of 2-arylpropionic esters by Candida rugosa and Rhizomucor miehei lipases.
abstract: Racemic arylpropionic esters 1-3, precursors of therapeutically important non-steroidal antiinflammatory drugs, were subjected to hydrolyses in the presence of either Candida rugosa or Rhizomucor miehei crude lipases. The hydrolyses of 1 and 2 proved to be highly enantioselective, whereas 3 was not transformed at all. Both the substrate specificity and the enantioselectivity of these lipases were explained through a molecular modeling study involving docking experiments between 1-3 and the amino acids forming the enzymes active-sites, whose three dimensional structures were obtained from X-ray crystallographic data, followed by extensive conformational analysis on their computer-generated complexes. The results of this study also account for the high enantioselective and good yielding hydrolysis of 3 (as the corresponding 2-chloroethyl ester) catalyzed by CRL pretreated with 2-propanol, recently reported in the literature, and lead to admit that such a treatment may operate very deep conformational changes on the amino acids of the enzyme active-site.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Botta
authors.forename: E
authors.initials: E
authors.lastname: Cernia
authors.forename: F
authors.initials: F
authors.lastname: Corelli
authors.forename: F
authors.initials: F
authors.lastname: Manetti
authors.forename: S
authors.initials: S
authors.lastname: Soro
mesh_terms: D001665:Binding Sites; D002175:Candida / Q000201:enzymology*; D018360:Crystallography, X-Ray; D007700:Kinetics; D008049:Lipase / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D009090:Mucorales / Q000201:enzymology*; D011422:Propionates / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D011422:Propionates; D008049:Lipase