2026-07-22T12:30:57Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/263532025-12-18T12:59:56Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617
Repisalud
author
Dubach, Victor R A
author
Segundo-Acosta, Pablo San
author
Murphy, Bonnie J
funder
Max Planck Society
2025-02-21T14:13:20Z
2025-02-21T14:13:20Z
2024-11
Dubach VRA, San Segundo-Acosta P, Murphy BJ. Structural and mechanistic insights into Streptococcus pneumoniae NADPH oxidase. Nat Struct Mol Biol. 2024 Nov;31(11):1769-1777.
10.1038/s41594-024-01348-w
1545-9985
1545-9993
Nature structural and molecular biology
39039317
https://hdl.handle.net/20.500.12105/26353
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.
eng
Structural and mechanistic insights into Streptococcus pneumoniae NADPH oxidase
research article
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