Mechanism of catalysis and inhibition of Mycobacterium tuberculosis SapM, implications for the development of novel antivirulence drugs.

ABSTRACT: Mycobacterium tuberculosis (Mtb) SapM is a secreted virulence factor critical for intracellular survival of the pathogen. The role of SapM in phagosome maturation arrest in host macrophages suggests its potential as a drug target to assist in the clearance of tuberculosis infection. However, the mechanism of action of SapM at the molecular level remains unknown. In this study, we provide new insights into the mechanism of catalysis, substrate specificity and inhibition of SapM, and we identify the critical residues for catalysis and substrate binding. Our findings demonstrate that SapM is an atypical monoester alkaline phosphatase, with a serine-based mechanism of catalysis probably metal-dependent. Particularly relevant to SapM function and pathogenesis, is its activity towards PI(4,5)P

SUBMITTER: Fernandez-Soto P 

PROVIDER: S-EPMC6635428 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature