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Structural modification of NADPH oxidase activator (Noxa 1) by oxidative stress: An experimental and computational

Pankaj Attri1, Jae-Hyun Park2, Joey De Backer3

  • 1Center of Plasma Nano-interface Engineering, Kyushu University, Fukuoka, Japan; Research group PLASMANT, Department of Chemistry, University of Antwerp, Belgium.

International Journal of Biological Macromolecules
|September 22, 2020
PubMed

Insights

Cold atmospheric plasma (CAP) alters the structure of Noxa1 SH3 protein, a key component of NADPH oxidases 1 (NOX1). This study investigates CAP

Area of Science:

  • Biophysics
  • Biochemistry
  • Cancer Research

Background:

  • NADPH oxidases 1 (NOX1) generate reactive oxygen species (ROS) implicated in cancer progression.
  • Noxa1 SH3 protein is a regulatory subunit of NOX1, influencing its activity.
  • Understanding protein structural changes is crucial for cancer signaling pathway research.

Purpose of the Study:

  • To investigate the structural modifications of Noxa1 SH3 protein induced by cold atmospheric plasma (CAP).
  • To explore the impact of CAP on NOX1 expression and cancer cell viability.
  • To elucidate the role of reactive oxygen and nitrogen species (RONS) in protein alteration.

Main Methods:

  • Purification and X-ray crystallography of Noxa1 SH3 protein.
  • Treatment of Noxa1 SH3 protein with two CAP reactors (pulsed dielectric barrier discharge and Soft Jet).
  • Analysis of structural deformation using circular dichroism, fluorescence, NMR spectroscopy, and molecular dynamics (MD) simulations.
  • Assessment of CAP effects on A375 cancer cell viability and NOX1 expression.

Main Results:

  • CAP treatment induced structural changes and deformation in Noxa1 SH3 protein.
  • Both DBD and Soft Jet CAP reactors demonstrated effects on protein structure.
  • CAP exposure influenced the viability and NOX1 expression in A375 cancer cells.

Conclusions:

  • CAP effectively induces structural modifications in Noxa1 SH3 protein.
  • The findings provide insights into protein oxidation by CAP-generated RONS.
  • This research contributes to understanding the potential of CAP in cancer research and therapy.
Keywords:
MD simulationsNoxa1 SH3Oxidative stressX-ray crystallography

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