6n14

Publication Abstract from PubMed

Mycobacterium tuberculosis, the pathogen responsible for tuberculosis (TB), is the leading cause of death from infectious disease worldwide. The class A serine beta-lactamase BlaC confers Mycobacterium tuberculosis resistance to conventional beta-lactam antibiotics. As the primary mechanism of bacterial resistance to beta-lactam antibiotics, the expression of a beta-lactamase by Mycobacterium tuberculosis results in hydrolysis of the beta-lactam ring and deactivation of these antibiotics. In this study, we conducted protein X-ray crystallographic analysis of the inactivation of BlaC, upon exposure to the inhibitor bis(benzoyl) phosphate. Crystal structure data confirms that serine beta-lactamase is phosphorylated at the catalytic serine residue (Ser-70) by this phosphate-based inactivator. This new crystallographic evidence suggests a mechanism for phosphorylation of BlaC inhibition by bis(benzoyl) phosphate over acylation. Additionally, we confirmed that bis(benzoyl) phosphate inactivated BlaC in a time-dependent manner.

Crystal Structure of Phosphoserine BlaC from Mycobacterium tuberculosis Inactivated by Bis(Benzoyl) Phosphate.,Moural TW, White DS, Choy CJ, Kang C, Berkman CE Int J Mol Sci. 2019 Jul 2;20(13). pii: ijms20133247. doi: 10.3390/ijms20133247. PMID:31269656^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.