8QT6

Cryo-EM structure of Streptococcus pneumoniae NADPH oxidase

8QT6 の概要

• エントリーDOI: 10.2210/pdb8qt6/pdb
• EMDBエントリー: 18644
• 分子名称: FAD-binding FR-type domain-containing protein, FLAVIN-ADENINE DINUCLEOTIDE, PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total)
• 機能のキーワード: nadph oxidase, ros producing, flavoprotein, heme protein, membrane protein
• 由来する生物種: Streptococcus pneumoniae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48079.08

構造登録者

Dubach, V.R.A.,San Segundo-Acosta, P.,Murphy, B.J. (登録日: 2023-10-12, 公開日: 2024-07-24, 最終更新日: 2024-11-27)

主引用文献

Dubach, V.R.A.,San Segundo-Acosta, P.,Murphy, B.J.
Structural and mechanistic insights into Streptococcus pneumoniae NADPH oxidase.
Nat.Struct.Mol.Biol., 31:1769-1777, 2024

PubMed Abstract: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) have a major role in the physiology of eukaryotic cells by mediating reactive oxygen species production. Evolutionarily distant proteins with the NOX catalytic core have been found in bacteria, including Streptococcus pneumoniae NOX (SpNOX), which is proposed as a model for studying NOXs because of its high activity and stability in detergent micelles. We present here cryo-electron microscopy structures of substrate-free and nicotinamide adenine dinucleotide (NADH)-bound SpNOX and of NADPH-bound wild-type and F397A SpNOX under turnover conditions. These high-resolution structures provide insights into the electron-transfer pathway and reveal a hydride-transfer mechanism regulated by the displacement of F397. We conducted structure-guided mutagenesis and biochemical analyses that explain the absence of substrate specificity toward NADPH and suggest the mechanism behind constitutive activity. Our study presents the structural basis underlying SpNOX enzymatic activity and sheds light on its potential in vivo function.

PubMed: 39039317
DOI: 10.1038/s41594-024-01348-w

実験手法

ELECTRON MICROSCOPY (2.29 Å)