Interdomain flexibility and interfacial integrity of β-lactamase inhibitory protein (BLIP) modulate its binding to class A β-lactamases.

ABSTRACT: β-Lactamase inhibitory protein (BLIP) consists of a tandem repeat of αβ domains conjugated by an interdomain loop and can effectively bind and inactivate class A β-lactamases, which are responsible for resistance of bacteria to β-lactam antibiotics. The varied ability of BLIP to bind different β-lactamases and the structural determinants for significant enhancement of BLIP variants with a point mutation are poorly understood. Here, we investigated the conformational dynamics of BLIP upon binding to three clinically prevalent class A β-lactamases (TEM1, SHV1, and PC1) with dissociation constants between subnanomolar and micromolar. Hydrogen deuterium exchange mass spectrometry revealed that the flexibility of the interdomain region was significantly suppressed upon strong binding to TEM1, b

SUBMITTER: Huang L 

PROVIDER: S-EPMC8363833 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature