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Hydrophilicity of heme derivatives influences site-specific tyrosine nitration in MnSOD

Huixian Ye1, Yiqing Liu2, Taiping Zhou2

  • 1Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan 430074, PR China; Key Laboratory of Jiangxi Province for Special Optoelectronic Artificial Crystal Materials, Institute of Applied Chemistry, School of Chemistry and Chemical Engineering, Jinggangshan University, Ji'an, Jiangxi 343009, PR China.

Journal of Inorganic Biochemistry
|June 8, 2026
PubMed

Insights

Catalyst hydrophilicity influences protein tyrosine nitration selectivity. Hydrophilic FeTPPS enhanced manganese superoxide dismutase (MnSOD) nitration at Tyr34 more than hydrophobic heme, impacting enzyme activity.

Area of Science:

  • Biochemistry
  • Oxidative Stress
  • Post-Translational Modifications

Background:

  • Tyrosine nitration is a key post-translational modification implicated in oxidative stress-related diseases.
  • Manganese superoxide dismutase (MnSOD) is susceptible to nitration at Tyr34, affecting its enzymatic activity.
  • The factors controlling tyrosine nitration site selectivity are not fully understood.

Purpose of the Study:

  • To investigate the role of nitrating catalyst hydrophilicity in determining tyrosine site selectivity.
  • To compare the nitration profiles of MnSOD induced by hydrophobic heme, hydrophilic FeTPPS, and a heme-hIAPP complex.

Main Methods:

  • Comparative analysis of MnSOD nitration using hydrophobic heme, hydrophilic FeTPPS, and heme-hIAPP complex.
  • Quantification of tyrosine nitration levels at specific sites, particularly Tyr34.
  • Enzyme activity assays and biophysical techniques (fluorescence spectroscopy, molecular docking) to assess binding and functional impact.

Main Results:

  • FeTPPS induced significantly higher Tyr34 nitration (40.1%) in MnSOD compared to peroxynitrite (23.6%), hydrophobic heme (16.8%), and heme-hIAPP (19.4%).
  • Nitration, particularly by FeTPPS, led to a substantial decrease in MnSOD enzymatic activity.
  • Molecular docking revealed distinct binding modes of heme and FeTPPS near Tyr34, with FeTPPS favoring electrostatic interactions and heme favoring hydrophobic contacts.

Conclusions:

  • Heme hydrophilicity is a critical determinant of protein tyrosine nitration selectivity.
  • Hydrophilic nitrating agents like FeTPPS can preferentially nitrate specific tyrosine residues, influencing protein function.
  • Understanding these selectivity principles is crucial for elucidating the role of nitration in disease pathogenesis.
Keywords:
HemeManganese superoxide dismutaseNitration site selectivityTyrosine nitration

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