Structural changes upon peroxynitrite-mediated nitration of peroxiredoxin 2; nitrated Prx2 resembles its disulfide-oxidized form.

Abstract : Peroxiredoxins are cys-based peroxidases that function in peroxide detoxification and H2O2-induced signaling. Human Prx2 is a typical 2-Cys Prx arranged as pentamers of head-to-tail homodimers. During the catalytic mechanism, the active-site cysteine (CP) cycles between reduced, sulfenic and disulfide state involving conformational as well as oligomeric changes. Several post-translational modifications were shown to affect Prx activity, in particular CP overoxidation which leads to inactivation. We have recently reported that nitration of Prx2, a post-translational modification on non-catalytic tyrosines, unexpectedly increases its peroxidase activity and resistance to overoxidation. To elucidate the cross-talk between this post-translational modification and the enzyme catalysis, we investigated the structural changes of Prx2 after nitration. Analytical ultracentrifugation, UV absorption, circular dichroism, steady-state and time-resolved fluorescence were used to connect catalytically relevant redox changes with tyrosine nitration. Our results show that the reduced nitrated Prx2 structurally resembles the disulfide-oxidized native form of the enzyme favoring a locally unfolded conformation that facilitates disulfide formation. These results provide structural basis for the kinetic analysis previously reported, the observed increase in activity and the resistance to overoxidation of the peroxynitrite-treated enzyme.
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Archives of Biochemistry and Biophysics, Elsevier, 2016, 590, pp.101-8. 〈10.1016/j.abb.2015.11.032〉
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Soumis le : lundi 3 avril 2017 - 16:30:50
Dernière modification le : mercredi 21 février 2018 - 17:10:02

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Lía Randall, Bruno Manta, Kimberly J Nelson, Javier Santos, Leslie B Poole, et al.. Structural changes upon peroxynitrite-mediated nitration of peroxiredoxin 2; nitrated Prx2 resembles its disulfide-oxidized form.. Archives of Biochemistry and Biophysics, Elsevier, 2016, 590, pp.101-8. 〈10.1016/j.abb.2015.11.032〉. 〈pasteur-01500776〉

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