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Crystal structure of BlaC from Mycobacterium tuberculosis bound to phosphateCrystal structure of BlaC from Mycobacterium tuberculosis bound to phosphate
Structural highlights
FunctionPublication Abstract from PubMedThe rise of multi- and even totally antibiotic resistant forms of Mycobacterium tuberculosis underlines the need for new antibiotics. The pathogen is resistant to beta-lactam compounds due to its native serine beta-lactamase, BlaC. This resistance can be circumvented by administration of a beta-lactamase inhibitor. We studied the interaction between BlaC and the inhibitor clavulanic acid. Our data show hydrolysis of clavulanic acid and recovery of BlaC activity upon prolonged incubation. The rate of clavulanic acid hydrolysis is much higher in the presence of phosphate ions. A specific binding site for phosphate is identified in the active site pocket, both in the crystalline state and in solution. NMR spectroscopy experiments show that phosphate binds to this site with a dissociation constant of 30 mM in the free enzyme. We conclude that inhibition of BlaC by clavulanic acid is reversible and that phosphate ions can promote the hydrolysis of the inhibitor. Phosphate Promotes the Recovery of Mycobacterium tuberculosis beta-Lactamase from Clavulanic Acid Inhibition.,Elings W, Tassoni R, van der Schoot SA, Luu W, Kynast JP, Dai L, Blok AJ, Timmer M, Florea BI, Pannu NS, Ubbink M Biochemistry. 2017 Nov 14. doi: 10.1021/acs.biochem.7b00556. PMID:29087696[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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