Crystal Structure of Phosphoserine BlaC from Mycobacterium tuberculosis Inactivated by Bis(Benzoyl) Phosphate.

ABSTRACT: Mycobacterium tuberculosis, the pathogen responsible for tuberculosis (TB), is the leading cause of death from infectious disease worldwide. The class A serine ?-lactamase BlaC confers Mycobacterium tuberculosis resistance to conventional ?-lactam antibiotics. As the primary mechanism of bacterial resistance to ?-lactam antibiotics, the expression of a ?-lactamase by Mycobacterium tuberculosis results in hydrolysis of the ?-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 ?-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.

SUBMITTER: Moural TW 

PROVIDER: S-EPMC6650796 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature