Analysis of the binding forces driving the tight interactions between beta-lactamase inhibitory protein-II (BLIP-II) and class A beta-lactamases.

ABSTRACT: ?-Lactamases hydrolyze ?-lactam antibiotics to provide drug resistance to bacteria. ?-Lactamase inhibitory protein-II (BLIP-II) is a potent proteinaceous inhibitor that exhibits low picomolar affinity for class A ?-lactamases. This study examines the driving forces for binding between BLIP-II and ?-lactamases using a combination of presteady state kinetics, isothermal titration calorimetry, and x-ray crystallography. The measured dissociation rate constants for BLIP-II and various ?-lactamases ranged from 10(-4) to 10(-7) s(-1) and are comparable with those found in some of the tightest known protein-protein interactions. The crystal structures of BLIP-II alone and in complex with Bacillus anthracis Bla1 ?-lactamase revealed no significant side-chain movement in BLIP-II in the complex versus the monomer. The structural rigidity of BLIP-II minimizes the loss of the entropy upon complex formation and, as indicated by thermodynamics experiments, may be a key determinant of the observed potent inhibition of ?-lactamases.

SUBMITTER: Brown NG 

PROVIDER: S-EPMC3173220 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature