4GAV

Structure of the Ndi1 protein from Saccharomyces cerevisiae in complex with quinone

Summary for 4GAV

• Entry DOI: 10.2210/pdb4gav/pdb
• Related: 4G9K 4GAP
• Descriptor: Rotenone-insensitive NADH-ubiquinone oxidoreductase, FLAVIN-ADENINE DINUCLEOTIDE, UBIQUINONE-2 (3 entities in total)
• Functional Keywords: nucleotide-binding domain, membrane, oxidoreductase
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side: P32340
• Total number of polymer chains: 2
• Total formula weight: 107809.04

Authors

Iwata, M.,Lee, Y.,Yamashita, T.,Yagi, T.,Iwata, S.,Cameron, A.D.,Maher, M.J. (deposition date: 2012-07-25, release date: 2012-09-05, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3 Å)