Ontology highlight
ABSTRACT:
SUBMITTER: Makarov V
PROVIDER: S-EPMC3958311 | biostudies-literature | 2014 Mar
REPOSITORIES: biostudies-literature
Makarov Vadim V Lechartier Benoit B Zhang Ming M Neres João J van der Sar Astrid M AM Raadsen Susanne A SA Hartkoorn Ruben C RC Ryabova Olga B OB Vocat Anthony A Decosterd Laurent A LA Widmer Nicolas N Buclin Thierry T Bitter Wilbert W Andries Koen K Pojer Florence F Dyson Paul J PJ Cole Stewart T ST
EMBO molecular medicine 20140205 3
The benzothiazinone lead compound, BTZ043, kills Mycobacterium tuberculosis by inhibiting the essential flavo-enzyme DprE1, decaprenylphosphoryl-beta-D-ribose 2-epimerase. Here, we synthesized a new series of piperazine-containing benzothiazinones (PBTZ) and show that, like BTZ043, the preclinical candidate PBTZ169 binds covalently to DprE1. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible ...[more]