6bdo

Structure of bacterial type II NADH dehydrogenase from Caldalkalibacillus thermarum complexed with a quinone inhibitor HQNO at 2.8A resolution

spinqualitylabelsall models 6bdo, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bdo is a 4 chain structure with sequence from Caldalkalibacillus thermarum TA2.A1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: FAD, HQO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F5L3B8_CALTT Publication Abstract from PubMed 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 complex structure, suggesting a conserved mechanism for quinone binding. Further, the structural analysis provided insight how modifications of quinolone scaffolds improve potency (e.g. quinolinyl pyrimidine derivatives) and suggests unexplored target space for the rational design of new NDH-2 inhibitors. Structure of the NDH-2 - HQNO inhibited complex provides molecular insight into quinone-binding site inhibitors.,Petri J, Shimaki Y, Jiao W, Bridges HR, Russell ER, Parker EJ, Aragao D, Cook GM, Nakatani Y Biochim Biophys Acta. 2018 Jul;1859(7):482-490. doi:, 10.1016/j.bbabio.2018.03.014. Epub 2018 Apr 3. PMID:29621505 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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