Architecture of the NADPH oxidase family of enzymes
Blessing C. Ogboo,
Uriy V. Grabovyy,
Aniket Maini,
Scott Scouten,
Albert van der Vliet,
Andrea Mattevi,
David E. Heppner
Affiliations
Blessing C. Ogboo
Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA
Uriy V. Grabovyy
Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA
Aniket Maini
Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA
Scott Scouten
Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA
Albert van der Vliet
Department of Pathology and Laboratory Medicine, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT, USA
Andrea Mattevi
Department of Genetics and Microbiology, University of Pavia, Italy
David E. Heppner
Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA; Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA; Corresponding author. Natural Sciences Complex. University at Buffalo, The State University of New York. Buffalo, NY, 14260, USA.
The NADPH Oxidases (NOX) catalyze the deliberate production of reactive oxygen species (ROS) and are established regulators of redox-dependent processes across diverse biological settings. Proper management of their activity is controlled through a conserved electron transfer (ET) cascade from cytosolic NADPH substrate through the plasma membrane to extracellular O2. After decades-long investigations of their biological functions, including potential as drug targets, only very recently has atomic-resolution information of NOX enzymes been made available. In this graphical review, we summarize the present structural biology understanding of the NOX enzymes afforded by X-ray crystallography and cryo-electron microscopy. Combined molecular-level insights predominantly informed by DUOX1 full-length Cryo-EM structures suggest a general structural basis for the control of their catalytic activity by intracellular domain-domain stabilization.
