4GAP

Structure of the Ndi1 protein from Saccharomyces cerevisiae in complex with NAD+

4GAP の概要

• エントリーDOI: 10.2210/pdb4gap/pdb
• 関連するPDBエントリー: 4G9K 4GAV
• 分子名称: Rotenone-insensitive NADH-ubiquinone oxidoreductase, FLAVIN-ADENINE DINUCLEOTIDE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: nucleotide-binding domains, membrane, 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: 108499.07

構造登録者

Iwata, M.,Lee, Y.,Yamashita, T.,Yagi, T.,Iwata, S.,Cameron, A.D.,Maher, M.J. (登録日: 2012-07-25, 公開日: 2012-09-05, 最終更新日: 2024-02-28)

主引用文献

Iwata, M.,Lee, Y.,Yamashita, T.,Yagi, T.,Iwata, S.,Cameron, A.D.,Maher, M.J.
The structure of the yeast NADH dehydrogenase (Ndi1) reveals overlapping binding sites for water- and lipid-soluble substrates.
Proc.Natl.Acad.Sci.USA, 109:15247-15252, 2012

PubMed Abstract: Bioenergy is efficiently produced in the mitochondria by the respiratory system consisting of complexes I-V. In various organisms, complex I can be replaced by the alternative NADH-quinone oxidoreductase (NDH-2), which catalyzes the transfer of an electron from NADH via FAD to quinone, without proton pumping. The Ndi1 protein from Saccharomyces cerevisiae is a monotopic membrane protein, directed to the matrix. A number of studies have investigated the potential use of Ndi1 as a therapeutic agent against complex I disorders, and the NDH-2 enzymes have emerged as potential therapeutic targets for treatments against the causative agents of malaria and tuberculosis. Here we present the crystal structures of Ndi1 in its substrate-free, NAD(+)- and ubiquinone- (UQ2) complexed states. The structures reveal that Ndi1 is a peripheral membrane protein forming an intimate dimer, in which packing of the monomeric units within the dimer creates an amphiphilic membrane-anchor domain structure. Crucially, the structures of the Ndi1-NAD(+) and Ndi1-UQ2 complexes show overlapping binding sites for the NAD(+) and quinone substrates.

PubMed: 22949654
DOI: 10.1073/pnas.1210059109

実験手法

X-RAY DIFFRACTION (2.9 Å)