Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193.

Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193.
Free Radic Biol Med. 2019 Jul 16;:
Authors: Randall LM, Rizza JD, Parsonage D, Santos J, Mehl RA, Lowther WT, Poole LB, Denicola A
Abstract
Peroxiredoxins (Prx) are enzymes that efficiently reduce hydroperoxides through active participation of cysteine residues (CP, CR). The first step in catalysis, the reduction of peroxide substrate, is fast, 107 - 108 M-1s-1 for human Prx2. In addition, the high intracellular concentration of Prx positions them not only as good antioxidants but also as central players in redox signaling pathways. These biological functions can be affected by post-translational modifications that could alter the peroxidase activity and/or interaction with other proteins. In particular, inactivation by hyperoxidation of CP, which occurs when a second molecule of peroxide reacts with the CP in the sulfenic acid form, modulates their participation in redox signaling pathways. The higher sensitivity to hyperoxidation of some Prx has been related to the presence of structural motifs that disfavor disulfide formation at the active site, making the CP sulfenic acid more available for hyperoxidation or interaction with a redox protein target. We previously reported that treatment of human Prx2 with peroxynitrite results in tyrosine nitration, a post-translational modification on non-catalytic residues, yielding a more active peroxidase ...

Source: Free Radical Biology and Medicine - July 15, 2019 Category: Biology Authors: Randall LM, Rizza JD, Parsonage D, Santos J, Mehl RA, Lowther WT, Poole LB, Denicola A Tags: Free Radic Biol Med Source Type: research