Document Type
Preprint
Publication Date
1-19-2022
Journal / Book Title
Chembiochem
Abstract
Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis, affects millions of people worldwide. Several TB drugs have lost efficacy due to emerging drug resistance and new anti-TB targets are needed. Recent research suggests that indole-3-glycerol phosphate synthase (IGPS) in M. tuberculosis (MtIGPS) could be such a target. IGPS is a (β/α)8-barrel enzyme that catalyzes the conversion of 1-(o-carboxyphenylamino)-1-deoxyribulose 5’-phosphate (CdRP) into indole-glycerol-phosphate (IGP) in the bacterial tryptophan biosynthetic pathway. M. tuberculosis over expresses the tryptophan pathway genes during an immune response and inhibition of MtIGPS allows CD4 T-cells to more effectively fight against M. tuberculosis. Here we review the published data on MtIGPS expression, kinetics, mechanism, and inhibition. We also discuss MtIGPS crystal structures and compare them to other IGPS structures to reveal potential structure-function relationships of interest for the purposes of drug design and biocatalyst engineering.
DOI
10.1002/cbic.202100314
Montclair State University Digital Commons Citation
Esposito, Nikolas; Konas, David W.; and Goodey, Nina M., "Indole-3-Glycerol Phosphate Synthase From Mycobacterium tuberculosis: A Potential New Drug Target" (2022). Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works. 632.
https://digitalcommons.montclair.edu/chem-biochem-facpubs/632
Rights
HHS Public Access Author manuscript. Published in final edited form as: Chembiochem. 2022 January 19; 23(2): e202100314. doi:10.1002/cbic.202100314.