Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Molecular dynamics simulations of the mononuclear zinc-beta-lactamase fromBacillus cereus complexed with benzylpenicillin and a quantum chemical study of the reaction mechanism
Autore:
Diaz, N; Suarez, D; Merz, KM;
Indirizzi:
Penn State Univ, Dept Chem, University Pk, PA 16802 USA Penn State Univ University Pk PA USA 16802 m, University Pk, PA 16802 USA Univ Oviedo, Dept Quim Fis & Analit, Oviedo 33006, Asturias, Spain Univ Oviedo Oviedo Asturias Spain 33006 it, Oviedo 33006, Asturias, Spain
Titolo Testata:
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
fascicolo: 40, volume: 123, anno: 2001,
pagine: 9867 - 9879
SICI:
0002-7863(20011010)123:40<9867:MDSOTM>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
SITE-DIRECTED MUTAGENESIS; MESH EWALD METHOD; ACTIVE-SITE; AB-INITIO; SEMIEMPIRICAL METHODS; BACTEROIDES-FRAGILIS; ANGSTROM RESOLUTION; ALKALINE HYDROLYZES; AUTOMATED DOCKING; CRYSTAL-STRUCTURE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
73
Recensione:
Indirizzi per estratti:
Indirizzo: Merz, KM Penn State Univ, Dept Chem, 152 Davey Lab, University Pk, PA 16802 USA Penn State Univ 152 Davey Lab University Pk PA USA 16802 6802 USA
Citazione:
N. Diaz et al., "Molecular dynamics simulations of the mononuclear zinc-beta-lactamase fromBacillus cereus complexed with benzylpenicillin and a quantum chemical study of the reaction mechanism", J AM CHEM S, 123(40), 2001, pp. 9867-9879

Abstract

Herein, we present results from MD simulations of the Michaelis complex formed between the B. cereus zinc-beta -lactamase enzyme and benzylpenicillin. The structural and dynamical effects induced by substrate-binding, the specific role of the conserved residues, and the near attack conformers of the Michaelis complex are discussed. Quantum chemical methods (HF/6-31G* and B3LYP/6-31G*) are also applied to study the hydrolysis reaction of N-methylazetidinone catalyzed by a monozinc system consisting of the side chains ofthe histidine residues (His86, His88, and His149) complexed with Zn-OH andthe side chains of Asp90 and His210. From this model system, we built molecular-mechanics representations of the prereactive complex and transition state configurations docked into the active site. Linear-scaling semiempirical calculations coupled with a continuum solvent model were then performed on these static models. We propose that the experimental rate data for the B. cereus enzyme is compatible with a one-step mechanism for the hydrolysisof beta -lactam substrates in which His210 acts as a proton donor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 09:46:22