Ontology highlight
ABSTRACT:
SUBMITTER: Shi C
PROVIDER: S-EPMC3222238 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
Journal of the American Chemical Society 20111024 45
BioA catalyzes the second step of biotin biosynthesis, and this enzyme represents a potential target to develop new antitubercular agents. Herein we report the design, synthesis, and biochemical characterization of a mechanism-based inhibitor (1) featuring a 3,6-dihydropyrid-2-one heterocycle that covalently modifies the pyridoxal 5'-phosphate (PLP) cofactor of BioA through aromatization. The structure of the PLP adduct was confirmed by MS/MS and X-ray crystallography at 1.94 Å resolution. Inact ...[more]