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Structural, thermodynamic and kinetic analysis of the picomolar binding affinity interaction of the beta-lactamase inhibitor protein-II (BLIP-II) with class A beta-lactamasesStructural, thermodynamic and kinetic analysis of the picomolar binding affinity interaction of the beta-lactamase inhibitor protein-II (BLIP-II) with class A beta-lactamases
Structural highlights
Publication Abstract from PubMedbeta-Lactamases hydrolyze beta-lactam antibiotics to provide drug resistance to bacteria. beta-Lactamase inhibitory protein-II (BLIP-II) is a potent proteinaceous inhibitor that exhibits low picomolar affinity for class A beta-lactamases. This study examines the driving forces for binding between BLIP-II and beta-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 beta-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 beta-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 beta-lactamases. Analysis of the binding forces driving the tight interactions between beta-lactamase inhibitory protein-II (BLIP-II) and class A beta-lactamases.,Brown NG, Chow DC, Sankaran B, Zwart P, Prasad BV, Palzkill T J Biol Chem. 2011 Sep 16;286(37):32723-35. Epub 2011 Jul 20. PMID:21775426[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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