Nitration transforms a sensitive peroxiredoxin 2 into a more active and robust peroxidase.

Area of Science:

• Biochemistry
• Cellular Biology
• Redox Signaling

Background:

• Peroxiredoxins (Prx) are crucial thiol-dependent peroxidases involved in hydrogen peroxide (H2O2)-induced redox signaling.
• Enzyme activity and signaling are affected by structural changes, including post-translational modifications like overoxidation, which can inactivate Prx.
• Nitrated Prx2 has been found in Alzheimer disease brains, suggesting a role in neurodegeneration.

Purpose of the Study:

• To characterize the effects of tyrosine nitration on Prx2.
• To investigate how tyrosine nitration impacts Prx2 activity, stability, and its role in redox signaling.

Main Methods:

• Treatment of disulfide-oxidized Prx2 with peroxynitrite.
• Mass spectrometry to identify nitration sites.
• Kinetic analyses to assess enzyme activity and stability.

Main Results:

• Peroxynitrite treatment resulted in mononitrated and dinitrated Prx2 species.
• Tyrosine 193, located in the C-terminal YF motif, was identified as a primary nitration site.
• Tyrosine nitration increased Prx2 peroxidase activity and resistance to overoxidation.
• Nitration facilitated intermolecular disulfide formation, enhancing enzyme robustness.

Conclusions:

• Tyrosine nitration of Prx2 is a novel post-translational modification that enhances enzyme activity and stability.
• Nitration at Tyrosine 193 protects the catalytic cysteine from oxidative inactivation.
• This modification represents a new mechanism for regulating Prx function within the complex redox signaling network.