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Assay Development for Identifying Inhibitors of the Mycobacterial FadD32 Activity
TLDR
The use of Tm (melting temperature) shift assay, which measures the modulation of FadD32 thermal stability, is described as a tool for the identification of potential ligands and for validation of compounds as inhibitors.
Development of a Microplate-Based Scintillation Proximity Assay for MraY Using a Modified Substrate
TLDR
The authors have developed a microplate-based homogeneous assay for MraY in which the product is captured on wheat germ agglutinin (WGA) scintillation proximity assay (SPA) beads and was validated by showing inhibition by specific inhibitors of MRAY but not by inhibitors of other enzymes of peptidoglycan synthesis.
Glycine and alanine dehydrogenase activities are catalyzed by the same protein in Mycobacterium smegmatis: upregulation of both activities under microaerophilic adaptation.
TLDR
The physiology of the fast-growing, nonpathogenic strain of Mycobacterium smegmatis ATCC 607 under low oxygen was studied by shifting the actively growing M. smegMatis cells to static microaerophilic growth conditions, which resulted in a similar phenomenon as seen with M. tuberculosis, i.e., elevated glycine dehydrogenase activity.
Screening, Identification, and Characterization of Mechanistically Diverse Inhibitors of the Mycobacterium Tuberculosis Enzyme, Pantothenate Kinase (CoaA)
TLDR
A high-throughput assay based on protein thermal melting to screen large numbers of compounds for hits with diverse MoI, which was confirmed through mechanistic studies that estimated Kie and Kies for representative compounds and through nuclear magnetic resonance–based ligand displacement assays.
Assessment of Mycobacterium tuberculosis Pantothenate Kinase Vulnerability through Target Knockdown and Mechanistically Diverse Inhibitors
TLDR
The synthesis and expansion efforts to understand the structure-activity relationships leading to the optimization of enzyme inhibition along with antimycobacterial activity established the poor vulnerability of PanK in M. tuberculosis.
Kinetic Modelling of GlmU Reactions – Prioritization of Reaction for Therapeutic Application
TLDR
It is demonstrated that in coupled model at low metabolite concentrations, inhibition of either of the GlmU reactions cause significant decrement in the overall Glm U rate, however at higher metabolites concentrations, rxn-2 showed higher decrement, and targeting uridyltranferase activity of MtuglmU would be a better choice for therapeutic intervention.
An assay for exogenous sources of purified MurG, enabled by the complementation of Escherichia coli murG(Ts) by the Mycobacterium tuberculosis homologue.
TLDR
The Mycobacterium tuberculosis murG gene, Rv2153, was expressed in Escherichia coli murG(Ts) strain OV58 on a plasmid under the control of the arabinose-inducible araBAD promoter, presenting an easy method to measure the activity of exogenous sources of MurG for structure-activity studies of mutant MurG proteins.