Putative 3D Structure of QcrB from Mycobacterium tuberculosis Cytochrome bc1 Complex, a Novel Drug-Target for New Series of Antituberculosis Agent Q203

Yoonae Ko (1) , Inhee Choi (1)

1 Institut Pasteur Korea - Institut Pasteur de Corée

Tuberculosis caused by Mycobacterium tuberculosis is still a serious world health problem. There is an urgent need for an effective drug against rapidly arising multiple-drug resistant M. tuberculosis (MDR-TB) and extensively drug resistant M. tuberculosis (XDR-TB) strains. Q203 was recently reported as the most promising M. tuberculosis agent, which is also active against MDR-TB and XDR-TB. The cyto-chrome b subunit of the cytochrome bc1 complex (QcrB) was identified as a drug target in M. tuberculosis (Rv2196) for Q203. Herein, we have built the homology models of M. tuberculosis QcrB WT and T313A mutants using the X-ray structures of other species' QcrB as templates: Rhodobacter sphaeroides, Paracoccus denitrificans, yeast and bovine. The model with the best quality based on the structural validation results was selected for docking and used for analyzing Q203-binding mode. These insightful information will be beneficial to the further development of imidazo pyridine amide series as novel antituberculosis drugs.

Keywords: Homology modeling; Protein–ligand docking; Tuberculosis; QcrB

Domains: Computer Science [cs]; Modeling and Simulation

Yoonae Ko, Inhee Choi. Putative 3D Structure of QcrB from Mycobacterium tuberculosis Cytochrome bc1 Complex, a Novel Drug-Target for New Series of Antituberculosis Agent Q203. Bulletin of the Korean Chemical Society, 2016, 37, pp.725-731. ⟨10.1002/bkcs.10765⟩. ⟨pasteur-01319758⟩