5ER0

Water-forming NADH oxidase from Lactobacillus brevis (LbNOX)

5ER0 の概要

• エントリーDOI: 10.2210/pdb5er0/pdb
• 分子名称: NADH oxidase, FLAVIN-ADENINE DINUCLEOTIDE, OXYGEN MOLECULE, ... (5 entities in total)
• 機能のキーワード: nadh oxidase, fad, molecular oxygen, oxidoreductase
• 由来する生物種: Lactobacillus brevis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 228529.90

構造登録者

Cracan, V.,Grabarek, Z. (登録日: 2015-11-13, 公開日: 2016-04-13, 最終更新日: 2023-09-27)

主引用文献

Titov, D.V.,Cracan, V.,Goodman, R.P.,Peng, J.,Grabarek, Z.,Mootha, V.K.
Complementation of mitochondrial electron transport chain by manipulation of the NAD+/NADH ratio.
Science, 352:231-235, 2016

PubMed Abstract: A decline in electron transport chain (ETC) activity is associated with many human diseases. Although diminished mitochondrial adenosine triphosphate production is recognized as a source of pathology, the contribution of the associated reduction in the ratio of the amount of oxidized nicotinamide adenine dinucleotide (NAD(+)) to that of its reduced form (NADH) is less clear. We used a water-forming NADH oxidase from Lactobacillus brevis (LbNOX) as a genetic tool for inducing a compartment-specific increase of the NAD(+)/NADH ratio in human cells. We used LbNOX to demonstrate the dependence of key metabolic fluxes, gluconeogenesis, and signaling on the cytosolic or mitochondrial NAD(+)/NADH ratios. Expression of LbNOX in the cytosol or mitochondria ameliorated proliferative and metabolic defects caused by an impaired ETC. The results underscore the role of reductive stress in mitochondrial pathogenesis and demonstrate the utility of targeted LbNOX for direct, compartment-specific manipulation of redox state.

PubMed: 27124460
DOI: 10.1126/science.aad4017

実験手法

X-RAY DIFFRACTION (2.406 Å)