Kinetic and Molecular -Modelling study of the interaction between Staphylococcus aureus PC1 enzyme and Imipenem

Show simple item record Vilanova Canet, Bartolomé Coll Parets, Miquel Frau Munar, Juan Muñoz Izquierdo, Francisco Donoso Pardo, Josefa Laurentina 2018-11-20T08:20:51Z
dc.description.abstract [eng] The interactions between imipenem (3), a clinically significant carbapenem antibiotic, and Staphylococcus aureus PC1 enzyme, were studied in detail. Imipenem behaves as a slow substrate that reacts by a branched pathway, which suggests the formation of a second acyl-enzyme intermediate. The individual microscopic rate constants for the process were determined. The results were analysed in the light of molecular-modelling considerations. Based on the analysis, the Ser-70(O ) group in the Michaelis-Menten complex formed between 3 and PC1 is very distant from the carbonyl group of the beta-lactam ring of 3, which is consistent with the decreased value of k2 (Model 2, see Scheme 2) for imipenem relative to an appropriate substrate such as benzylpenicillin (2). The deacylation is the rate-determining step of the turnover process. This can be ascribed to the fact that in the deacylation of the second acyl-enzyme, the H2O molecule lying closest to the ester group, Wat81, is in an unfavorable orientation to hydrolyse the intermediate.
dc.format application/pdf
dc.relation.isformatof Versió preprint del document publicat a:
dc.relation.ispartof Helvetica Chimica Acta, 2001, vol. 84, p. 3366-3379
dc.subject.classification 54 - Química
dc.subject.other 54 - Chemistry. Crystallography. Mineralogy
dc.title Kinetic and Molecular -Modelling study of the interaction between Staphylococcus aureus PC1 enzyme and Imipenem
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/submittedVersion 2018-11-20T08:20:51Z info:eu-repo/date/embargoEnd/2075-01-01
dc.embargo 2075-01-01
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess

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