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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The Peroxidatic Thiol of Peroxiredoxin 1 is Nitrosated by Nitrosoglutathione but Coordinates to the Dinitrosyl Iron Complex of Glutathione

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Author(s):
Truzzi, Daniela R. [1] ; Alves, V, Simone ; Netto, Luis E. S. [2] ; Augusto, Ohara [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo - Brazil
[2] Alves, Simone, V, Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, BR-05508090 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: ANTIOXIDANTS; v. 9, n. 4 APR 2020.
Web of Science Citations: 0
Abstract

Protein S-nitrosation is an important consequence of NOBLACK CIRCLE center dot metabolism with implications in physiology and pathology. The mechanisms responsible for S-nitrosation in vivo remain debatable and kinetic data on protein S-nitrosation by different agents are limited. 2-Cys peroxiredoxins, in particular Prx1 and Prx2, were detected as being S-nitrosated in multiple mammalian cells under a variety of conditions. Here, we investigated the kinetics of Prx1 S-nitrosation by nitrosoglutathione (GSNO), a recognized biological nitrosating agent, and by the dinitrosyl-iron complex of glutathione (DNIC-GS; {[}Fe(NO)(2)(GS)(2)](-)), a hypothetical nitrosating agent. Kinetics studies following the intrinsic fluorescence of Prx1 and its mutants (C83SC173S and C52S) were complemented by product analysis; all experiments were performed at pH 7.4 and 25 celcius. The results show GSNO-mediated nitrosation of Prx1 peroxidatic residue (k+NOCys52 = 15.4 +/- 0.4 M-1. s(-1)) and of Prx1 Cys(83) residue (k+NOCys83 = 1.7 +/- 0.4 M-1. s(-1)). The reaction of nitrosated Prx1 with GSH was also monitored and provided a second-order rate constant for Prx1Cys(52)NO denitrosation of k-NOCys52 = 14.4 +/- 0.3 M-1. s(-1). In contrast, the reaction of DNIC-GS with Prx1 did not nitrosate the enzyme but formed DNIC-Prx1 complexes. The peroxidatic Prx1 Cys was identified as the residue that more rapidly replaces the GS ligand from DNIC-GS (kDNICCys52 = 7.0 +/- 0.4 M-1. s(-1)) to produce DNIC-Prx1 ({[}Fe(NO)(2)(GS)(Cys(52)-Prx1)](-)). Altogether, the data showed that in addition to S-nitrosation, the Prx1 peroxidatic residue can replace the GS ligand from DNIC-GS, forming stable DNIC-Prx1, and both modifications disrupt important redox switches. (AU)

FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC