Structural and biochemical characterization of compounds inhibiting Mycobacterium tuberculosis pantothenate kinase.

ABSTRACT: Mycobacterium tuberculosis, the bacterial causative agent of tuberculosis, currently affects millions of people. The emergence of drug-resistant strains makes development of new antibiotics targeting the bacterium a global health priority. Pantothenate kinase, a key enzyme in the universal biosynthesis of the essential cofactor CoA, was targeted in this study to find new tuberculosis drugs. The biochemical characterizations of two new classes of compounds that inhibit pantothenate kinase from M. tuberculosis are described, along with crystal structures of their enzyme-inhibitor complexes. These represent the first crystal structures of this enzyme with engineered inhibitors. Both classes of compounds bind in the active site of the enzyme, overlapping with the binding sites of the natural s

SUBMITTER: Bjorkelid C 

PROVIDER: S-EPMC3689968 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature