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.

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 Molecular Identification and Characterization of an Essential Pyruvate Transporter from Trypanosoma brucei

2013 ◽  
Vol 288 (20) ◽  
pp. 14428-14437 ◽  
Author(s):  
Marco A. Sanchez
Keyword(s):  
Trypanosoma Brucei ◽  
Drug Target ◽  
Life Cycle Stage ◽  
Bloodstream Form ◽  
Potential Drug Target ◽  
High Affinity ◽  
Physiological Relevance ◽  
First Time ◽  
Identification And Characterization

Pyruvate export is an essential physiological process for the bloodstream form of Trypanosoma brucei as the parasite would otherwise accumulate this end product of glucose metabolism to toxic levels. In the studies reported here, genetic complementation in Saccharomyces cerevisiae has been employed to identify a gene (TbPT0) that encodes this vital pyruvate transporter from T. brucei. Expression of TbPT0 in S. cerevisiae reveals that TbPT0 is a high affinity pyruvate transporter. TbPT0 belongs to a clustered multigene family consisting of five members, whose expression is up-regulated in the bloodstream form. Interestingly, TbPT family permeases are related to polytopic proteins from plants but not to characterized monocarboxylate transporters from mammals. Remarkably, inhibition of the TbPT gene family expression in bloodstream parasites by RNAi is lethal, confirming the physiological relevance of these transporters. The discovery of TbPT0 reveals for the first time the identity of the essential pyruvate transporter and provides a potential drug target against the mammalian life cycle stage of T. brucei.

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

scholarly journals Newly Discovered Cell Shape Promoting Protein Complex Involved in the Maintenance of Distinct Helical Shape of Helicobacter Pylori

2019 ◽  
pp. 28-30
Author(s):  
Freeman Paczkowski
Keyword(s):  
Cell Wall ◽  
Helicobacter Pylori ◽  
Cell Shape ◽  
Drug Target ◽  
Clinical Implications ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Multiple Cell ◽  
H Pylori ◽  
Cell Shape Formation

The distinct helical shape of the bacterium Helicobacter Pylori (H. pylori) assists this organism in colonizing the digestive organs of its target host. It has been discovered that a key determinant of helical cell shape formation in H. pylori is the Csd5 protein, which engages in multiple cell shape promoting interactions with the cell wall and other various proteins. This finding has significant clinical implications, as it outlines Csd5 as a potential drug target for treating H. pylori infection in the future.

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