Publication

Structural studies suggest a peptidoglycan hydrolase function for the Mycobacterium tuberculosis Tat-secreted protein Rv2525c

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Structural Basis for Benzothiazinone-Mediated Killing of Mycobacterium tuberculosis

Paul Joseph Dyson, Stewart Cole, John McKinney, Neeraj Dhar, Florence Pojer, Joao Pedro De Almeida Neres, Elizabeth Fullam

The benzothiazinone BTZ043 is a tuberculosis drug candidate with nanomolar whole-cell activity. BTZ043 targets the DprE1 catalytic component of the essential enzyme decaprenylphosphoryl-beta-D-ribofuranose-2'-epimerase, thus blocking biosynthesis of arabin ...

American Association for the Advancement of Science2012

Structure and function of the transketolase from Mycobacterium tuberculosis and comparison with the human enzyme

Stewart Cole, Florence Pojer, Elizabeth Fullam

The transketolase (TKT) enzyme in Mycobacterium tuberculosis represents a novel drug target for tuberculosis treatment and has low homology with the orthologous human enzyme. Here, we report on the structural and kinetic characterization of the transketola ...

Royal Soc2012

Structural Studies and Protein Engineering of Human O6-Alkylguanine-DNA Alkyltransferase

Birgit Mollwitz

The specific labeling of proteins with synthetic probes is a powerful approach to study protein function and protein tags have been widely used for this purpose. A well-established example for a self-labeling protein tag is SNAP-tag. It specifically reacts ...

EPFL2012

Cholesterol Catabolism by Mycobacterium tuberculosis Requires Transcriptional and Metabolic Adaptations

John McKinney

To understand the adaptation of Mycobacterium tuberculosis to the intracellular environment, we used comprehensive metabolite profiling to identify the biochemical pathways utilized during growth on cholesterol, a critical carbon source during chronic infe ...

2012

DprE1 as a Drug Target from Mycobacterium Tuberculosis

Claudia Trefzer

Benzothiazinones (BTZs) form a new class of potent antimycobacterial agents with a minimal inhibitory concentration of 1 ng/mL against Mycobacterium tuberculosis. Although the target of BTZs has been identified as decaprenylphosphoryl--D-ribose 2- oxidase ...

EPFL2012

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The proteins belonging to the WhiB superfamily are small global transcriptional regulators typical of actinomycetes. In this paper, we characterize the role of WhiB5, a Mycobacterium tuberculosis protein belonging to this superfamily. A null mutant was con ...

American Society for Microbiology2012

ESAT-6 secretion-independent impact of ESX-1 genes espF and espG1 on virulence of Mycobacterium tuberculosis

Stewart Cole, Jeffrey Chen

The pathogenesis of Mycobacterium tuberculosis largely depends on the secretion of the 6-kD early secreted antigenic target ESAT-6 (EsxA) and the 10-kD culture filtrate protein CFP-10 (EsxB) via the ESX-1/typeVII secretion system. Although gene products fr ...

Oxford University Press2011

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ESAT-6 system 1 (ESX-1)-mediated secretion in Mycobacterium tuberculosis is dependent on proteins encoded by the cotranscribed espA-espC-espD gene cluster. While the roles of EspA and EspC with respect to the ESX-1 secretion system have been actively inves ...

2011

Biological and structural characterization of the Mycobacterium smegmatis nitroreductase NfnB, and its role in benzothiazinone resistance

Stewart Cole, Joao Pedro De Almeida Neres, Giulia Manina

Summary Tuberculosis is still a leading cause of death in developing countries, for which there is an urgent need for new pharmacological agents. The synthesis of the novel antimycobacterial drug class of benzothiazinones (BTZs) and the identification of t ...

2010

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Benzothiazinones (BTZs) form a new class of potent antimycobacterial agents. Although the target of BTZs has been identified as decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1), their detailed mechanism of action remains obscure. Here we demonstrate th ...

American Chemical Society2010