β-lactamase Inhibition

The monobactam antibiotic aztreonam is used to treat cystic fibrosis patients with chronic pulmonary infections colonized by bacterial Pseudomonas strains which express β-lactamases. Several active site residues in class A β-lactamases have been proposed to play key roles in monobactam hydrolysis. Leighton Coates et al. at Oak Ridge National Laboratory used neutron and high-resolution X-ray crystallography to probe the mechanism by which β-lactamases hydrolyze monobactam antibiotics.

Publication: Active-Site Protonation States in an Acyl-Enzyme Intermediate of a Class A β-Lactamase with a Monobactam Substrate. Venu Gopal Vandavasi et al. Antimicrobial Agents and Chemotherapy