Dynamics of Protein Tyrosine Nitration and Denitration: A Review

Stress is a situation in which the cellular redox homoeostasis is altered because of excessive production of different reactive species eg. reactive oxygen species (ROS), reactive nitrogen species (RNS) [1]. The stress which is mediated by ROS like singlet oxygen, superoxide, H2O2 and hydroxyl radicals known as oxidative stress [2]. ROS are produced during cell cycle progression, cell differentiation, cell signaling [3,4]. It can damage the macromolecules like membrane lipids [5], proteins [6] and DNA [7]. In analogy to oxidative stress, the term `nitrosative stress' involves reactive nitrogen species (RNS) where the ratio of nitrosants to antioxidants is >1. RNS are produced due to the reaction of ROS with Nitric oxide (NO•). During nitrosative stress different types of RNS cause nitrosylation of biomolecules thereby creating an imbalance in the production and the exclusion of reactive nitrogen and oxygen intermediates of the body [8]. One of the major marker of nitrosative stress is the formation of 3-Nitrotyrosine (NO2-TYR), a stable post-translational modification of protein. In vivo it forms due to the reaction between tyrosine residues and nitrating agents. During the formation of 3-Nitotyrosine a nitro group (-NO2) is added in the ortho position of the phenolic hydroxyl group of tyrosine. Mostly the natural abundance of tyrosine residues is about 3% in proteins. Tyrosine may be nitrated through numerous chemical reactions. This modification introduces a net negative charge at neutral pH, which triggers changes in the local physiological and chemical environment of the biomolecule. Nitration of tyrosine residues often indicates loss of protein activity. Alteration of the structure and function of protein due to formation of nitrated tyrosine may change the rate of proteolytic degradation [9]. Moreover presence of high amount of RNS or non-functional antioxidant systems, target proteins can also be nitrated at specific tyrosine residues [10]. Introduction Dynamics of Protein Tyrosine Nitration and Denitration: A Review