Efficient inhibition of class A and class D beta-lactamases by Michaelis complexes.
J Biol Chem
; 282(30): 21588-91, 2007 Jul 27.
Article
en En
| MEDLINE
| ID: mdl-17561511
ABSTRACT
A 6-alkylidiene penam sulfone, SA-1-204, is an efficient inhibitor of both SHV-1 and OXA-1 beta-lactamases with K(I) = 42 +/- 4 nm and 1.0 +/- 0.1 microm, respectively. To gain insight into the reaction chemistry of SA-1-204, the reactions between this inhibitor and SHV-1 and OXA-1 were studied by Raman spectroscopy in single crystals and in solution. Raman signatures characteristic of the unreacted beta-lactam ring show that in both phases the inhibitor binds as a noncovalent Michaelis-like complex. This complex is present as the major population for periods of up to an hour. On longer time scales, the Raman data show that beta-lactam ring opening eventually leads to a complex mixture of reaction products. However, the data clearly demonstrate that the key species for inhibition on the time scale of bacterial half-lives is the noncovalent complex preceding acylation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de beta-Lactamasas
Idioma:
En
Revista:
J Biol Chem
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos