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Showing results 1 to 5 of 5

Journal article

A Fragment-based approach to assess the ligandability of ArgB, ArgC, ArgD and ArgF in the L-arginine biosynthetic pathway of Mycobacterium tuberculosis

Authors : Gupta, Pooja (2021)

The L-arginine biosynthesis pathway consists of eight enzymes that catalyse the conversion of L- glutamate to L-arginine, appears to be attractive target for anti-Tuberculosis (TB) drug discovery. Starvation of M. tuberculosis deleted for either argB or argF genes led to rapid sterilization of these strains in mice while Chemical inhibition of ArgJ with Pranlukast was also found to clear chronic M. tuberculosis infection in animal models. In this wo...

Ebooks (Sách điện tử)

Chemical inhibition of histidine biosynthesis curtails M. tuberculosis infection

Authors : Tiwari, Satish (2023)

To overcome the drug resistance crisis and shorten the current duration of human tuberculosis (TB) therapy, new anti-TB molecules is required. In an earlier study, we have shown that Mycobacterium tuberculosis (Mtb), the causative agent of TB, with a fractured de novo histidine biosynthesis fails to mount TB infection in mouse model, emboldening that disrupting the function of this pathway may constitute a novel strategy to curtailing TB infection.&...

Journal article

Fortuitous in vitro compound degradation produces a tractable hit against Mycobacterium tuberculosis dethiobiotin synthetase: a cautionary tale of what goes in, does not always come out

Authors : Salaemae, Wanisa (2023)

A molecule flagged in an in silico docking screen against MtDTBS, was inadvertently hydrolysed in the crystal conditions used for hit validation. The resulting fragment-sized molecule bound to the DAPA substrate binding pocket of the target enzyme (MtDTBS) with millimolar affinity, as measured by surface plasmon resonance, but was later modified to a highly potent (nanomolar) ligand and promising lead for the development of novel tuberculos...

Journal article

High-throughput, fluorescent-aptamer-based measurements of steady-state transcription rates for Mycobacterium tuberculosis RNA polymerase

Authors : Jensen, Drake (2023)

The first step in gene expression is the transcription of DNA sequences into RNA. Regulation at the level of transcription leads to changes in steady-state concentrations of RNA transcripts, affecting the flux of downstream functions and ultimately cellular phenotypes. Changes in transcript levels are routinely followed in cellular contexts via genome-wide sequencing techniques. However, in vitro mechanistic studies of transcription have lagged with ...

Journal Article

Protein engineering, production, reconstitution in lipid nanoparticles, and initial characterization of the Mycobacterium tuberculosis EfpA drug exporter

Authors : Ishola, Olamide (2023)

Mycobacterium tuberculosis (Mtb) drug exporters contribute an efficient mechanism for drug resistance. Therefore, understanding the structure–function relationship in these proteins is important. We focused on the Mtb EfpA efflux pump, which belongs to the major facilitator superfamily (MSF) and transports anti-tuberculosis drugs outside the bacterial cell. Here, we report on our advancements in producing and in vitro characterization of this protein. We engineered a c...