Structure and mechanisms of ROS generation by NADPH oxidases

Curr Opin Struct Biol. 2019 Dec:59:91-97. doi: 10.1016/ Epub 2019 Apr 30.


NADPH oxidases (NOXs) are integral membrane enzymes that produce reactive oxygen species. Humans have seven NOX enzymes that feature a very similar catalytic core but distinct regulatory mechanisms. The recent structural elucidation of the NOX catalytic domains has been a step forward in the field. NADPH, FAD, and two hemes form a linear array of redox cofactors that transfer electrons across to the two sides of the membrane. Oxygen is reduced through an unusual outer sphere mechanism that does not involve any covalent intermediate with the heme iron. Several recent studies have expanded the roles of NOXs in cell signaling, innate immune response, and cell proliferation including oncogenic transformation. This work reinforces NOX-generated ROS as powerful signaling molecules. A challenging question is to understand the specific mechanisms of enzyme regulation and to harness the growing insight on NOXs' structure and biochemistry to generate more powerful small-molecule modulators of NOX activities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Proliferation
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • NADPH Oxidases / chemistry*
  • NADPH Oxidases / metabolism
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Oxidation-Reduction
  • Oxygen / chemistry
  • Protein Binding
  • Reactive Oxygen Species / chemistry*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Structure-Activity Relationship


  • Reactive Oxygen Species
  • NADPH Oxidases
  • Oxygen