6PQ9

Crystal Structure of TLA-1 S70G extended spectrum Beta-lactamase

Summary for 6PQ9

• Entry DOI: 10.2210/pdb6pq9/pdb
• Descriptor: Beta-lactamase, ASPARTIC ACID, ACETATE ION, ... (6 entities in total)
• Functional Keywords: lactamase, antibiotic, resistance, hidrolase, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 34168.95

Authors

Rudino-Pinera, E.,Cifuentes-Castro, V.H.,Rodriguez-Alamazan, C. (deposition date: 2019-07-08, release date: 2019-12-11, Last modification date: 2023-10-11)

Primary citation

Cifuentes-Castro, V.,Rodriguez-Almazan, C.,Silva-Sanchez, J.,Rudino-Pinera, E.
The crystal structure of ESBL TLA-1 in complex with clavulanic acid reveals a second acylation site.
Biochem.Biophys.Res.Commun., 522:545-551, 2020

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

PubMed: 31780261
DOI: 10.1016/j.bbrc.2019.11.138

Experimental method

X-RAY DIFFRACTION (2.191 Å)