+
検索条件

キーワード
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

-
Structure paper

タイトル	Structural and mechanistic insights into Streptococcus pneumoniae NADPH oxidase.
ジャーナル・号・ページ	Nat Struct Mol Biol, Year 2024
掲載日	2024年7月22日
著者	Victor R A Dubach / Pablo San Segundo-Acosta / Bonnie J Murphy /
PubMed 要旨	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 ...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.
リンク	Nat Struct Mol Biol / PubMed:39039317
手法	EM (単粒子)
解像度	2.2 - 2.64 Å
構造データ	18644 8qt6 EMDB-18644, PDB-8qt6: Cryo-EM structure of Streptococcus pneumoniae NADPH oxidase 手法: EM (単粒子) / 解像度: 2.29 Å 18645 8qt7 EMDB-18645, PDB-8qt7: Cryo-EM structure of Streptococcus pneumoniae NADPH oxidase in complex with NADPH 手法: EM (単粒子) / 解像度: 2.2 Å 18646 8qt9 EMDB-18646, PDB-8qt9: Cryo-EM structure of stably reduced Streptococcus pneumoniae NADPH oxidase in complex with NADH 手法: EM (単粒子) / 解像度: 2.36 Å 18647 8qta EMDB-18647, PDB-8qta: Cryo-EM structure of Streptococcus pneumoniae NADPH oxidase F397A mutant in complex with NADPH 手法: EM (単粒子) / 解像度: 2.64 Å
化合物	ChemComp-FAD: FLAVIN-ADENINE DINUCLEOTIDE / FAD / FADYM ChemComp-HEM: PROTOPORPHYRIN IX CONTAINING FE ChemComp-HOH: WATER ChemComp-NDP: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / NADPH ChemComp-NAI*: 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE / NADH
由来	streptococcus pneumoniae (肺炎レンサ球菌)
キーワード	MEMBRANE PROTEIN / NADPH oxidase / ROS producing / flavoprotein / heme protein