Role of E166 in the imine to enamine tautomerization of the clinical beta-lactamase inhibitor sulbactam.
Biochemistry
; 48(43): 10196-8, 2009 Nov 03.
Article
em En
| MEDLINE
| ID: mdl-19791797
ABSTRACT
Mechanism-based inhibitors of class A beta-lactamases, such as sulbactam, undergo a complex series of chemical reactions in the enzyme active site. Formation of a trans-enamine acyl-enzyme via a hydrolysis-prone imine is responsible for transient inhibition of the enzyme. Although the imine to enamine tautomerization is crucial to inhibition of the enzyme, there are no experimental data to suggest how this chemical transformation is catalyzed in the active site. In this report, we show that E166 acts as a general base to promote the imine to enamine tautomerization.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulbactam
/
Inibidores Enzimáticos
/
Inibidores de beta-Lactamases
/
Aminas
/
Iminas
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos