Related Experiment Video

Updated: Jun 26, 2025

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
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Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells

Published on: March 16, 2017

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Structural basis of human NOX5 activation

Chenxi Cui1, Meiqin Jiang1, Nikhil Jain1

  • 1Department of Structural Biology, St Jude Children's Research Hospital, Memphis, TN38105, USA.

Nature Communications
|May 11, 2024
PubMed

Insights

Calcium binding to NADPH oxidase 5 (NOX5) activates superoxide production by increasing NADPH dynamics. This study reveals the molecular basis of NOX5 activation and its role in diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • NADPH oxidase 5 (NOX5) produces superoxide radicals, impacting sperm motility and cardiac rhythm.
  • NOX5 overexpression is linked to cancers, diabetes, and cardiovascular diseases.
  • The molecular mechanism of NOX5 activation by calcium signaling, specifically electron transfer, remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism of NOX5 activation by calcium.
  • To understand how calcium binding triggers electron transfer from NADPH to FAD.
  • To investigate the structural basis of NOX5 stability and enzymatic activity.

Main Methods:

  • Single-particle cryogenic electron microscopy (cryo-EM) to capture NOX5 motions.
  • Biochemical assays and mutagenesis analyses.
  • Molecular dynamics (MD) simulations.

Main Results:

  • Calcium binding to the EF-hand domain enhances NADPH dynamics.
  • Increased NADPH dynamics facilitate electron transfer to FAD, leading to superoxide production.
  • A novel zinc-binding motif crucial for NOX5 stability and activity was identified.

Conclusions:

  • Calcium binding is the key activator of NOX5-mediated superoxide production.
  • Structural insights reveal the mechanism of NOX5 activation and ROS modulation.
  • Understanding NOX5 activation provides targets for treating related diseases.

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