Isochorismate Synthase (MenF)-3D Prediction in Mycobacterium Tuberculosis: A Potential Drug Target

2017 ◽  
Vol 5 (2) ◽  
pp. 117
Author(s):  
Leeladhar Sammatur ◽  
C.M. Anuradha ◽  
Srinivasulu Cheemanapalli ◽  
P. Madhusudana ◽  
Suresh Kumar Chitta
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Isochorismate Synthase

scholarly journals Inhibition of Glutamine Synthetase: A Potential Drug Target in Mycobacterium tuberculosis

Molecules ◽  
2014 ◽  
Vol 19 (9) ◽  
pp. 13161-13176 ◽  
Author(s):  
Sherry Mowbray ◽  
Muthu Kathiravan ◽  
Abhishek Pandey ◽  
Luke Odell
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Glutamine Synthetase ◽  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug

scholarly journals Biosynthesis of the redox cofactor mycofactocin comprises oligoglycosylation by MftF in Mycolicibacterium smegmatis

2019 ◽  
Author(s):  
Luis Peña-Ortiz ◽  
Ana Patrícia Graça ◽  
Huijuan Guo ◽  
Daniel Braga ◽  
Tobias G. Köllner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Metabolic Profiling ◽  
Drug Target ◽  
Structure Elucidation ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Alcohol Metabolism ◽  
Future Studies ◽  
Mycobacterial Diseases

AbstractMycofactocin (MFT) is a redox cofactor involved in alcohol metabolism of mycobacteria including Mycobacterium tuberculosis. In recent years, a preliminary biosynthetic model of MFT has been established by in-vitro studies, while the final structure of MFT remained elusive. Here, we report the discovery of MFT by metabolomics and establish a model of its biosynthesis in Mycolicibacterium smegmatis. Structure elucidation revealed that MFT is decorated with up to nine β-1,4-linked glucose residues. Dissection of biosynthetic genes demonstrated that the oligoglycosylation is catalyzed by the glycosyltransferase MftF. Furthermore, we confirm the cofactor function of MFT by activity-based metabolic profiling using the carveol dehydrogenase LimC and show that the MFT pool expands during cultivation on ethanol. Our results close an important gap of knowledge, will guide future studies into the physiological roles of MFT in bacteria and may inspire its utilization as a biomarker or potential drug target to combat mycobacterial diseases.

scholarly journals Chemical validation of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase using fragment linking and CRISPR interference

2020 ◽  
Author(s):  
Jamal El Bakali ◽  
Michal Blaszczyk ◽  
Joanna C. Evans ◽  
Jennifer A. Boland ◽  
William J. McCarthy ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Crystal Structures ◽  
Active Site ◽  
Drug Target ◽  
Potential Drug Target ◽  
Biosynthesis Pathway ◽  
Potential Drug ◽  
Antimicrobial Drugs ◽  
X Ray ◽  
Crispr Interference

AbstractThe coenzyme A (CoA) biosynthesis pathway has attracted attention as a potential target for much-needed novel antimicrobial drugs, including for the treatment of tuberculosis (TB), the lethal disease caused by Mycobacterium tuberculosis (Mtb). Seeking to identify the first inhibitors of Mtb phosphopantetheine adenylyltransferase (MtbPPAT), the enzyme that catalyses the penultimate step in CoA biosynthesis, we performed a fragment screen. In doing so, we discovered three series of fragments that occupy distinct regions of the MtbPPAT active site, presenting a unique opportunity for fragment linking. Here we show how, guided by X-ray crystal structures, we could link weakly-binding fragments to produce an active site binder with a KD < 20 μM and on-target anti-Mtb activity, as demonstrated using CRISPR interference. This study represents a big step toward validating MtbPPAT as a potential drug target and designing a MtbPPAT-targeting anti-TB drug.Abstract Figure

Proteome-wide subtractive approach to prioritize a hypothetical protein of XDR-Mycobacterium tuberculosis as potential drug target

2019 ◽  
Vol 41 (11) ◽  
pp. 1281-1292 ◽  
Author(s):  
Reaz Uddin ◽  
Quratulain Nehal Siddiqui ◽  
Muhammad Sufian ◽  
Syed Sikander Azam ◽  
Abdul Wadood
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Target ◽  
Hypothetical Protein ◽  
Potential Drug Target ◽  
Potential Drug

scholarly journals Oxidative phosphorylation — A potential drug target in Mycobacterium tuberculosis

2014 ◽  
Vol 1837 ◽  
pp. e126-e127
Author(s):  
Dean C. Crick ◽  
Ashutosh Upadhyay ◽  
Fabio Fontes ◽  
Michael R. McNeil ◽  
Mary Jackson
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Oxidative Phosphorylation ◽  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug

scholarly journals Identification and Characterization of a Major Cell Wall-Associated Iron-Regulated Envelope Protein (Irep-28) in Mycobacterium tuberculosis

2006 ◽  
Vol 13 (10) ◽  
pp. 1137-1142 ◽  
Author(s):  
Veena C. Yeruva ◽  
Sridevi Duggirala ◽  
V. Lakshmi ◽  
Daniel Kolarich ◽  
Friedrich Altmann ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Envelope Protein ◽  
Drug Target ◽  
Iron Limitation ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Tuberculosis Patients ◽  
Identification And Characterization

ABSTRACTIron limitation and the expression of mycobactin and carboxymycobactin byMycobacterium tuberculosisare known. Here, we report how iron regulated the coordinate expression of these two siderophores and a 28-kDa cell wall-associated iron-regulated protein (Irep-28). Irep-28 is identified as the DNA-binding HU homologue HupB protein (hupB[Rv2986c]). Antibodies to this protein were detected in sera from tuberculosis patients. The location of the protein in the cell wall makes it a potential drug target.

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