MptpA Kinetics Enhanced by Allosteric Control of an Active Conformation.

ABSTRACT: Understanding allostery in the Mycobacterium tuberculosis low molecular weight protein tyrosine phosphatase (MptpA) is a subject of great interest since MptpA is one of two protein tyrosine phosphatases (PTPs) from the pathogenic organism Mycobacterium tuberculosis expressed during host cell infection. Here, we combine computational modeling with solution NMR spectroscopy and we find that Q75 is an allosteric site. Removal of the polar side chain of Q75 by mutation to leucine results in a cascade of events that reposition the acid loop over the active site and relocates the catalytic aspartic acid (D126) at an optimal position for proton donation to the leaving aryl group of the substrate and for subsequent hydrolysis of the thiophosphoryl intermediate. The computational analysis is consis

SUBMITTER: Maschietto F 

PROVIDER: S-EPMC10623291 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature