Related Experiment Video
Updated: Jun 26, 2025
08:32
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
Summary
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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