Molecular dynamics simulations of the mononuclear zinc-beta-lactamase from Bacillus cereus.
J Am Chem Soc
; 123(16): 3759-70, 2001 Apr 25.
Article
en En
| MEDLINE
| ID: mdl-11457108
Herein, we report molecular dynamics simulations of the mononuclear form of the Bacillus cereuszinc-beta-lactamase. We studied two different configurations which differ in the presence of a zinc-bound hydroxide or a zinc-bound water and in the protonation state of the essential His210 residue. Contacts of the catalytically important residues (Asp90, His210, Cys168, etc.) with the zinc center are characterized by the MD analyses. The nature of the Zn-OH(2) --> His210 proton transfer pathway connecting the two configurations was studied by means of QM calculations on cluster models while the relative stability of the two configurations was estimated from QM/MM calculations in the enzyme. From these results, a theoretical model for the kinetically active form of the B. cereus metalloenzyme is proposed. Some mechanistic implications and the influence of mutating the Cys168 residue are also discussed.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bacillus cereus
/
Zinc
/
Beta-Lactamasas
/
Metaloproteínas
Idioma:
En
Revista:
J Am Chem Soc
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos