Biology subjects

Gore, G.

Publications and source records attributed to Gore, G..

3 recordsLinked to original sources

bioRxiv2025

Cefdinir binding to a class-A β-lactamase revealed by serial cryo-crystallography

One of the most common resistance mechanisms against antibiotics employed by Gram-negative bacteria involves the production of {beta}-lactamases, resulting in rapid hydrolysis of the antibiotic. Extensive use of the early generation cephalosporins led to the rise of extended-spectrum {beta}-lactamases (ESBLs) like CTX-Ms. Cefdinir is an extended-spectrum third-generation cephalosporin administered since the late 90s; despite this, there is no reported 3D-structure of the antibiotic bound to any {beta}-lactamase or Penicillin-Binding-Protein (PBP) in the PDB. Here we report the X-ray crystallographic structure of Cefdinir-bound CTX-M-14 E166A mutant obtained via serial cryo-crystallography (cryo-SSX). SynopsisSerial cryo-crystallography reveals the structure of the extended spectrum {beta}-lactamase CTX-M-14, in complex with the third-generation cephalosporin antibiotic Cefdinir.

biophysics↗

bioRxiv2025

Binding mode of isoxazolyl penicillins to a Class-A beta-lactamase at ambient conditions

The predominant resistance mechanism observed in Gram-negative bacteria involves the production of {beta}-lactamases, which catalyse the hydrolysis of {beta}-lactam antibiotics, thereby rendering them ineffective. Although isoxazolyl penicillins are available since the 1970s, there are currently no structures in complex with class-A {beta}-lactamases available. In order to support the rational development of new {beta}-lactamase inhibitors, we have analysed the structure of the clinically relevant {beta}-lactamase CTX-M-14 from Klebsiella pneumoniae near physiolog- ical temperatures. By utilizing serial synchrotron crystallography, we demonstrate the acyl-enzyme intermediates of the catalytically impaired CTX-M-14 mutant E166A in complex with three isoxazolyl penicillins: oxacillin, cloxacillin and dichloxacillin. While the three derivatives differ only by one and two Cl atoms, respectively, they show marked differences in their binding mode.

biochemistry↗

bioRxiv2022

Millisecond cryo-trapping by the spitrobot crystal plunger simplifies time-resolved crystallography

We introduce the spitrobot, a protein crystal plunger, enabling reaction quenching via cryo-trapping with millisecond time-resolution. Canonical micromesh loops are mounted on an electropneumatic piston, reactions are initiated via the liquid application method (LAMA), and finally intermediate states are cryo-trapped in liquid nitrogen. We demonstrate binding of several ligands in microcrystals of three enzymes, and trapping of reaction intermediates and conformational changes in macroscopic crystals of tryptophan synthase.

biophysics↗