Why the extended-spectrum [beta]-lactamases SHV-2 and SHV-5 are 'hypersusceptible' to mechanism-based inhibitors

A comparative analysis of the intermediates formed by compounds tazobactam, sulbactam, and clavulanic acid with wild-type (WT) SHV-1 [beta]-lactamase and its extended-spectrum [beta]-lactamase (ESBL) variants SHV-2 and SHV-5, which carry the G238S and G238S/E240K substitutions was carried out to understand the hypersusceptible of ESBLs. A Raman spectroscopic analysis of the reactions in single crystals showed that, compared to WT, the SHV-2 and SHV-5 variants have relatively higher populations of the stable trans-enamine intermediate over the less stable and more easily hydrolyzable cis-enamine and imine co-intermediates.