The crystal structure of ESBL TLA-1 in complex with clavulanic acid reveals a second acylation site.
Biochem Biophys Res Commun
; 522(2): 545-551, 2020 02 05.
Article
en En
| MEDLINE
| ID: mdl-31780261
ß-lactamases are the main molecules responsible for giving bacterial resistance against ß-lactam antibiotics. The study of ß-lactamases has allowed the development of antibiotics capable of inhibiting these enzymes. In this context, extended spectrum ß-lactamase (ESBL) TLA-1 has spread in Escherichia coli and Enterobacter cloacae clinical isolates during the last 30 years in Mexico. In this research, the 3D structures of ESBL TLA-1 and TLA-1 S70G mutant, both ligand-free and in complex with clavulanic acid were determined by X-ray crystallography. Four clavulanic acid molecules were found in the structure of TLA-1, two of those were intermediaries of the acylation process and were localized covalently bound to two different amino acid residues, Ser70 and Ser237. The coordinates of TLA-1 in complex with clavulanic acid shows the existence of a second acylation site, additional to Ser70, which might be extendable to several members of the subclass A ß-lactamases family. This is the first time that two serines involved in binding clavulanic acid has been reported and described to an atomic level.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Beta-Lactamasas
/
Ácido Clavulánico
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2020
Tipo del documento:
Article
País de afiliación:
México
Pais de publicación:
Estados Unidos