3QHY

Structural, thermodynamic and kinetic analysis of the picomolar binding affinity interaction of the beta-lactamase inhibitor protein-II (BLIP-II) with class A beta-lactamases

Summary for 3QHY

• Entry DOI: 10.2210/pdb3qhy/pdb
• Related: 1JTD 1JTG 3QI0
• Descriptor: Beta-lactamase, Beta-lactamase inhibitory protein II (3 entities in total)
• Functional Keywords: enyzme-inhibitor complex, beta-propeller, beta-lactamase, protein:protein interaction, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Bacillus anthracis (anthrax,anthrax bacterium); More
• Total number of polymer chains: 2
• Total formula weight: 58120.56

Authors

Brown, N.G.,Chow, D.C.,Sankaran, B.,Zwart, P.,Prasad, B.V.V.,Palzkill, T.,Berkeley Structural Genomics Center (BSGC) (deposition date: 2011-01-26, release date: 2011-07-20, Last modification date: 2023-09-13)

Primary citation

Brown, N.G.,Chow, D.C.,Sankaran, B.,Zwart, P.,Prasad, B.V.,Palzkill, T.
Analysis of the binding forces driving the tight interactions between beta-lactamase inhibitory protein-II (BLIP-II) and class A beta-lactamases.
J.Biol.Chem., 286:32723-32735, 2011

PubMed Abstract: β-Lactamases hydrolyze β-lactam antibiotics to provide drug resistance to bacteria. β-Lactamase inhibitory protein-II (BLIP-II) is a potent proteinaceous inhibitor that exhibits low picomolar affinity for class A β-lactamases. This study examines the driving forces for binding between BLIP-II and β-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 β-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 β-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 β-lactamases.

PubMed: 21775426
DOI: 10.1074/jbc.M111.265058

Experimental method

X-RAY DIFFRACTION (2.06 Å)