Structure of the NDH-2 - HQNO inhibited complex provides molecular insight into quinone-binding site inhibitors.

ABSTRACT: Type II NADH:quinone oxidoreductase (NDH-2) is a proposed drug-target of major pathogenic microorganisms such as Mycobacterium tuberculosis and Plasmodium falciparum. Many NDH-2 inhibitors have been identified, but rational drug development is impeded by the lack of information regarding their mode of action and associated inhibitor-bound NDH-2 structure. We have determined the crystal structure of NDH-2 complexed with a quinolone inhibitor 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO). HQNO is nested into the slot-shaped tunnel of the Q-site, in which the quinone-head group is clamped by Q317 and I379 residues, and hydrogen-bonds to FAD. The interaction of HQNO with bacterial NDH-2 is very similar to the native substrate ubiquinone (UQ₁) interactions in the yeast Ndi1-UQ₁

SUBMITTER: Petri J 

PROVIDER: S-EPMC6167311 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature