4G74

Crystal structure of NDH with Quinone

4G74 の概要

• エントリーDOI: 10.2210/pdb4g74/pdb
• 関連するPDBエントリー: 4G6G 4G6H 4G73
• 分子名称: Rotenone-insensitive NADH-ubiquinone oxidoreductase, mitochondrial, 2,3-DIMETHOXY-5-METHYL-6-(3,11,15,19-TETRAMETHYL-EICOSA-2,6,10,14,18-PENTAENYL)-[1,4]BENZOQUINONE, FRAGMENT OF TRITON X-100, ... (6 entities in total)
• 機能のキーワード: rossmann fold, electron transfer, fad, oxidoreductase
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast)
• 細胞内の位置: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side: P32340
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 117487.62

構造登録者

Li, W.,Feng, Y.,Ge, J.,Yang, M. (登録日: 2012-07-19, 公開日: 2012-10-24, 最終更新日: 2023-11-08)

主引用文献

Feng, Y.,Li, W.,Li, J.,Wang, J.,Ge, J.,Xu, D.,Liu, Y.,Wu, K.,Zeng, Q.,Wu, J.W.,Tian, C.,Zhou, B.,Yang, M.
Structural insight into the type-II mitochondrial NADH dehydrogenases.
Nature, 491:478-482, 2012

PubMed Abstract: The single-component type-II NADH dehydrogenases (NDH-2s) serve as alternatives to the multisubunit respiratory complex I (type-I NADH dehydrogenase (NDH-1), also called NADH:ubiquinone oxidoreductase; EC 1.6.5.3) in catalysing electron transfer from NADH to ubiquinone in the mitochondrial respiratory chain. The yeast NDH-2 (Ndi1) oxidizes NADH on the matrix side and reduces ubiquinone to maintain mitochondrial NADH/NAD(+) homeostasis. Ndi1 is a potential therapeutic agent for human diseases caused by complex I defects, particularly Parkinson's disease, because its expression restores the mitochondrial activity in animals with complex I deficiency. NDH-2s in pathogenic microorganisms are viable targets for new antibiotics. Here we solve the crystal structures of Ndi1 in its substrate-free, NADH-, ubiquinone- and NADH-ubiquinone-bound states, to help understand the catalytic mechanism of NDH-2s. We find that Ndi1 homodimerization through its carboxy-terminal domain is critical for its catalytic activity and membrane targeting. The structures reveal two ubiquinone-binding sites (UQ(I) and UQ(II)) in Ndi1. NADH and UQ(I) can bind to Ndi1 simultaneously to form a substrate-protein complex. We propose that UQ(I) interacts with FAD to act as an intermediate for electron transfer, and that NADH transfers electrons through this FAD-UQ(I) complex to UQ(II). Together our data reveal the regulatory and catalytic mechanisms of Ndi1 and may facilitate the development or targeting of NDH-2s for potential therapeutic applications.

PubMed: 23086143
DOI: 10.1038/nature11541

実験手法

X-RAY DIFFRACTION (2.48 Å)