INVESTIGADORES
VILA Alejandro Jose
artículos
Título:
Substrate binding to mononuclear metallo-beta-lactamase from Bacillus cereus
Autor/es:
DAL PERARO, M; VILA, AJ; CARLONI, P
Revista:
PROTEINS: STRUCTURE, FUNCTION AND GENETICS
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Año: 2004 vol. 54 p. 412 - 423
ISSN:
0887-3585
Resumen:
Structure and dynamics of substrate binding (cefotaxime) to the catalytic pocket of the mononuclear zinc--lactamase from Bacillus cereus are investigated by molecular dynamics simulations. The calculations, which are based on the hydrogen-bond pattern recently proposed by Dal Peraro et al. (J Biol Inorg Chem 2002; 7:704?712), are carried out for both the free and the complexed enzyme. In the resting state, active site pattern and temperature B-factors are in agreement with crystallographic data. In the complexed form, cefotaxime is accommodated into a stable orientation in the catalytic pocket within the nanosecond timescale, interacting with the enzyme zinc-bound hydroxide and the surrounding loops. The -lactam ring remains stable and very close to the hydroxide nucleophile agent, giving a stable representation of the productive enzyme-substrate complex.
