The role of beta-lactam carboxyl group on binding of penicillins and cephalosporins to Class C beta-lactamases

Show simple item record Fenollar-Ferrer, Cristina Frau Munar, Juan Donoso Pardo, Josefa Laurentina Muñoz Izquierdo, Francisco 2018-10-11T11:10:51Z
dc.description.abstract [eng] Molecular models for the Henry Michaelis complexes of Enterobacter cloacae, a class C beta-lactamase, with penicillin G and cephalotin have been constructed by using molecular mechanic calculations, based on the AMBER force field, to examine the molecular differentiation mechanisms between cephalosporins and penicillins in -lactamases. Ser318Ala and Thr316Ala mutations in both complexes and Asn346Ala and Thr316Ala/Asn346Ala double mutation in penicillin G complex have also been studied. Results confirm that Thr316, Ser318, and Asn346 play a crucial role in the substrate recognition, via their interactions with one of the oxygens of the antibiotic carboxyl group. Both mutation Ser318Ala and Thr316Ala strongly affect the correct binding of cephalotin to P99, the first mainly by precluding the discriminating salt bridge between carboxyl and serine OH groups, and the second one by the Ser318, Lys315, and Tyr150 spatial rearrangements. On the other hand, Ser318Ala mutation has little effect on penicillin G binding, but the Thr316Ala/Asn346Ala double mutation causes the departure of the antibiotic from the oxyanion hole. Molecular dynamic simulations allow us to interpret the experimental results of some class C and A beta-lactamases.
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dc.relation.ispartof Proteins-Structure Function And Bioinformatics, 2003, vol. 51, p. 442-452
dc.rights , 2003
dc.subject.classification 54 - Química
dc.subject.other 54 - Chemistry. Crystallography. Mineralogy
dc.title The role of beta-lactam carboxyl group on binding of penicillins and cephalosporins to Class C beta-lactamases
dc.type info:eu-repo/semantics/article 2018-10-11T11:10:51Z 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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