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- W4317815462 abstract "DprE2 is an essential enzyme in the synthesis of decaprenylphosphoryl-β-d-arabinofuranose (DPA) and subsequently arabinogalactan, and is a significant new drug target for M. tuberculosis. Two compounds from the GSK-177 box set, GSK301A and GSK032A, were identified through Mt-DprE2-target overexpression studies. The Mt-DprE1-DprE2 complex was co-purified and a new in vitro DprE2 assay developed, based on the oxidation of the reduced nicotinamide adenine dinucleotide cofactor of DprE2 (NADH/NADPH). The Mt-DprE1-DprE2 complex showed interesting kinetics in both the DprE1 resazurin-based assay, where Mt-DprE2 was found to enhance Mt-DprE1 activity and reduce substrate inhibition; and also in the DprE2 assay, which similarly exhibited substrate inhibition and a difference in kinetics of the two potential cofactors, NADH and NADPH. Although, no inhibition was observed in the DprE2 assay by the two GSK set compounds, spontaneous mutant generation indicated a possible explanation in the form of a pro-drug activation pathway, involving fgd1 and fbiC." @default.
- W4317815462 created "2023-01-24" @default.
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- W4317815462 date "2023-01-30" @default.
- W4317815462 modified "2023-10-16" @default.
- W4317815462 title "Assay development and inhibition of the Mt-DprE2 essential reductase from Mycobacterium tuberculosis" @default.
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- W4317815462 doi "https://doi.org/10.1099/mic.0.001288" @default.
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