6BDO

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

6BDO の概要

• エントリーDOI: 10.2210/pdb6bdo/pdb
• 関連するPDBエントリー: 4NWZ 5WED
• 分子名称: FAD-dependent pyridine nucleotide-disulfide oxidoreductase, FLAVIN-ADENINE DINUCLEOTIDE, 2-HEPTYL-4-HYDROXY QUINOLINE N-OXIDE, ... (4 entities in total)
• 機能のキーワード: rossmann fold, nadh dehydrogenase, oxidoreductase, flavo protein, membrane protein, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• 由来する生物種: Caldalkalibacillus thermarum TA2.A1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 181948.84

構造登録者

Cook, G.M.,Aragao, D.,Nakatani, Y. (登録日: 2017-10-23, 公開日: 2018-05-16, 最終更新日: 2023-10-25)

主引用文献

Petri, J.,Shimaki, Y.,Jiao, W.,Bridges, H.R.,Russell, E.R.,Parker, E.J.,Aragao, D.,Cook, G.M.,Nakatani, Y.
Structure of the NDH-2 - HQNO inhibited complex provides molecular insight into quinone-binding site inhibitors.
Biochim. Biophys. Acta, 1859:482-490, 2018

PubMed 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 (UQ) interactions in the yeast Ndi1-UQ 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.

PubMed: 29621505
DOI: 10.1016/j.bbabio.2018.03.014

実験手法

X-RAY DIFFRACTION (2.8 Å)