3-Nitrotyrosine and related derivatives in proteins: precursors, radical intermediates and impact in function

CAMPOLO, NICOLÁS; ISSOGLIO, FEDERICO M.; ESTRIN, DARÍO A.; BARTESAGHI, SILVINA; RADI, RAFAEL

ESSAYS IN BIOCHEMISTRY

PORTLAND PRESS LTD

Año: 2020 vol. 64 p. 111 - 133

0071-1365

Oxidative post-translational modification of proteins by molecular oxygen (O2)- and nitricoxide (?NO)-derived reactive species is a usual process that occurs in mammalian tissuesunder both physiological and pathological conditions and can exert either regulatory or cytotoxiceffects. Although the side chain of several amino acids is prone to experience oxidativemodifications, tyrosine residues are one of the preferred targets of one-electron oxidants,given the ability of their phenolic side chain to undergo reversible one-electron oxidationto the relatively stable tyrosyl radical. Naturally occurring as reversible catalytic intermediatesat the active site of a variety of enzymes, tyrosyl radicals can also lead to the formationof several stable oxidative products through radical?radical reactions, as is the case of3-nitrotyrosine (NO2Tyr). The formation of NO2Tyr mainly occurs through the fast reactionbetween the tyrosyl radical and nitrogen dioxide (?NO2). One of the key endogenous nitratingagents is peroxynitrite (ONOO−), the product of the reaction of superoxide radical (O2?−)with ?NO, but ONOO−-independent mechanisms of nitration have been also disclosed. Thischemical modification notably affects the physicochemical properties of tyrosine residuesand because of this, it can have a remarkable impact on protein structure and function, bothin vitro and in vivo. Although low amounts of NO2Tyr are detected under basal conditions,significantly increased levels are found at pathological states related with an overproductionof reactive species, such as cardiovascular and neurodegenerative diseases, inflammationand aging. While NO2Tyr is a well-established stable oxidative stress biomarker and a goodpredictor of disease progression, its role as a pathogenic mediator has been laboriouslydefined for just a small number of nitrated proteins and awaits further studies.