title: Substrate binding to mononuclear metallo-beta-lactamase from Bacillus cereus.
abstract: Structure and dynamics of substrate binding (cefotaxime) to the catalytic pocket of the mononuclear zinc-beta-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 beta-lactam ring remains stable and very close to the hydroxide nucleophile agent, giving a stable representation of the productive enzyme-substrate complex.
authors.affiliation: International School for Advanced Studies, SISSA and INFM-DEMOCRITOS, Trieste, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Dal Peraro
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Vila
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D001409:Bacillus cereus / Q000201:enzymology*; D001665:Binding Sites; D002384:Catalysis; D002439:Cefotaxime / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D009038:Motion; D011485:Protein Binding; D055672:Static Electricity; D013379:Substrate Specificity; D013696:Temperature; D015032:Zinc / Q000378:metabolism; D001618:beta-Lactamases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008667:Metalloproteins; D001618:beta-Lactamases; D015032:Zinc; D002439:Cefotaxime