5KMS

The structure of type II NADH dehydrogenase from Caldalkalibacillus thermarum complexed with NAD+ at 2.5 angstrom resolution.

5KMS の概要

• エントリーDOI: 10.2210/pdb5kms/pdb
• 関連するPDBエントリー: 5KMP 5KMQ 5KMR
• 分子名称: FAD-dependent pyridine nucleotide-disulfide oxidoreductase, FLAVIN-ADENINE DINUCLEOTIDE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: rossmann fold, nadh dehydrogenase, oxidoreductase
• 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: 182093.58

構造登録者

Cook, G.M.,Aragao, D.,Nakatani, Y. (登録日: 2016-06-27, 公開日: 2017-02-01, 最終更新日: 2023-10-25)

主引用文献

Blaza, J.N.,Bridges, H.R.,Aragao, D.,Dunn, E.A.,Heikal, A.,Cook, G.M.,Nakatani, Y.,Hirst, J.
The mechanism of catalysis by type-II NADH:quinone oxidoreductases.
Sci Rep, 7:40165-40165, 2017

PubMed Abstract: Type II NADH:quinone oxidoreductase (NDH-2) is central to the respiratory chains of many organisms. It is not present in mammals so may be exploited as an antimicrobial drug target or used as a substitute for dysfunctional respiratory complex I in neuromuscular disorders. NDH-2 is a single-subunit monotopic membrane protein with just a flavin cofactor, yet no consensus exists on its mechanism. Here, we use steady-state and pre-steady-state kinetics combined with mutagenesis and structural studies to determine the mechanism of NDH-2 from Caldalkalibacillus thermarum. We show that the two substrate reactions occur independently, at different sites, and regardless of the occupancy of the partner site. We conclude that the reaction pathway is determined stochastically, by the substrate/product concentrations and dissociation constants, and can follow either a ping-pong or ternary mechanism. This mechanistic versatility provides a unified explanation for all extant data and a new foundation for the development of therapeutic strategies.

PubMed: 28067272
DOI: 10.1038/srep40165

実験手法

X-RAY DIFFRACTION (2.5 Å)