Indole‐3‐Glycerol Phosphate Synthase From Mycobacterium tuberculosis : A Potential New Drug Target
| Autor: | David W. Konas, Nina M. Goodey, Nikolas Esposito |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
Tuberculosis ATP synthase biology Organic Chemistry Tryptophan Indole-3-Glycerol-Phosphate Synthase Drug resistance medicine.disease biology.organism_classification Biochemistry Microbiology Mycobacterium tuberculosis Enzyme chemistry medicine biology.protein Molecular Medicine Molecular Biology Pathogen |
| Zdroj: | ChemBioChem. 23 |
| ISSN: | 1439-7633 1439-4227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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