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Published on: June 21, 2021
Structural basis of protein oxidation resistance: a lysozyme study
Marion Girod1, Quentin Enjalbert2, Claire Brunet2
1Université de Lyon, 69622, Lyon, France; Institut des Sciences Analytiques, UMR 5280, CNRS, Université Claude Bernard Lyon 1, Lyon, France.
Protein structure influences oxidative damage resistance. Molecular dynamics simulations reveal that unfolded protein regions and exposed amino acids are more susceptible to radiation-induced oxidation, impacting cellular function and aging.
Area of Science:
- Biochemistry
- Structural Biology
- Aging Research
Background:
- Oxidative damage to proteins is linked to aging and cellular dysfunction.
- Native, folded protein structures exhibit inherent resistance to oxidation.
- Understanding protein oxidation is crucial for comprehending aging mechanisms.
Purpose of the Study:
- To investigate the structural basis of protein resistance to radiation-induced oxidation.
- To compare oxidative damage susceptibility in native versus misfolded lysozyme.
- To identify structural determinants of protein oxidation.
Main Methods:
- Utilized chicken egg white lysozyme in native and misfolded states.
- Employed targeted tandem mass spectrometry to analyze tryptic fragments.
- Performed molecular dynamics (MD) simulations to compute structural parameters.
Main Results:
- Oxidative damage followed a two-step decay process: initial amino acid oxidation and subsequent protein degradation.
- Higher root-mean-square deviation (RMSD) correlated with increased susceptibility to oxidative modification.
- Amino acid side-chain involvement in hydrogen bonds conferred protection against oxidation.
- Greater solvent exposure of side chains increased susceptibility to oxidation and fragmentation.
Conclusions:
- Protein structure significantly dictates susceptibility to radiation-induced oxidation.
- Structural parameters like RMSD and solvent exposure are key indicators of oxidation vulnerability.
- Combined structural insights provide a comprehensive understanding of protein oxidation mechanisms.
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