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Publication Abstract from PubMed

beta-lactamases are the main molecules responsible for giving bacterial resistance against beta-lactam antibiotics. The study of beta-lactamases has allowed the development of antibiotics capable of inhibiting these enzymes. In this context, extended spectrum beta-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 beta-lactamases family. This is the first time that two serines involved in binding clavulanic acid has been reported and described to an atomic level.

The crystal structure of ESBL TLA-1 in complex with clavulanic acid reveals a second acylation site.,Cifuentes-Castro V, Rodriguez-Almazan C, Silva-Sanchez J, Rudino-Pinera E Biochem Biophys Res Commun. 2019 Nov 25. pii: S0006-291X(19)32266-1. doi:, 10.1016/j.bbrc.2019.11.138. PMID:31780261^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.