Fragment-based exploration of binding site flexibility in Mycobacterium tuberculosis BioA.

ABSTRACT: The PLP-dependent transaminase (BioA) of Mycobacterium tuberculosis and other pathogens that catalyzes the second step of biotin biosynthesis is a now well-validated target for antibacterial development. Fragment screening by differential scanning fluorimetry has been performed to discover new chemical scaffolds and promote optimization of existing inhibitors. Calorimetry confirms binding of six molecules with high ligand efficiency. Thermodynamic data identifies which molecules bind with the enthalpy driven stabilization preferred in compounds that represent attractive starting points for future optimization. Crystallographic characterization of complexes with these molecules reveals the dynamic nature of the BioA active site. Different side chain conformational states are stabilized in r

SUBMITTER: Dai R 

PROVIDER: S-EPMC4687966 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature