Modeling of the metallo-beta-lactamase from B-fragilis: Structural and dynamic effects of inhibitor binding

Citation
Fr. Salsbury et al., Modeling of the metallo-beta-lactamase from B-fragilis: Structural and dynamic effects of inhibitor binding, PROTEINS, 44(4), 2001, pp. 448-459
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEINS-STRUCTURE FUNCTION AND GENETICS
ISSN journal
0887-3585 → ACNP
Volume
44
Issue
4
Year of publication
2001
Pages
448 - 459
Database
ISI
SICI code
0887-3585(20010901)44:4<448:MOTMFB>2.0.ZU;2-N
Abstract
The structure and dynamics of an inhibitor-bound complex of the metallo-bet a -lactamase from Bacteroides fragilis are studied by using molecular dynam ics. A search of the conformational space was performed to obtain three dis tinct models of the complex, which were then subjected to solvated molecula r dynamics. A solvated molecular dynamics study of the apo protein was perf ormed to serve as a baseline for comparison with the bound simulations. We find loop conformation changes due to binding as well as a decrease in flex ibility of the protein as a whole and especially in the major loop of the b eta -lactamase. We report the structural and dynamical features of the inhi bitor-bound and apo, models, as well as experimentally measurable quantitie s, which should be capable of distinguishing the two binding modes we have determined. Proteins 2001;44:448-459. (C) 2001 Wiley-Liss,Inc.