Protein oxidation an overview of metabolism of sulphur containing amino acid cysteine

Abstract

The available data suggest that among cellular constituents, proteins are the major target for oxidation primarily because of their quantity and high rate of interactions with ROS. Proteins are susceptible to ROS modifications of amino acid side chains which alter protein structure. Among the amino acids, Cysteine (Cys) is more prone to oxidation by ROS because of its high nucleophilic property. The reactivity of Cys with ROS is due to the presence of thiol group. In the oxidised form, Cys forms disulfide bond, which are primary covalent cross-link found in proteins, and which stabilize the native conformation of a protein. Indirect evidence suggests that thiol modifications by ROS may be involved in neurodegenerative disorders, but the significance and precise extent of the contributions are poorly understood. Here, we review the role of oxidized Cys in different pathological consequences and its biochemistry may increase the research in the discovery of new therapies. The purpose of this review is to re-examine the role and biochemistry of oxidised Cys residues.

The crosstalk of NAD, ROS and autophagy in cellular health and ageing

“…Protein modification by ROS and RNS constitutes a covalent modification of amino acid residues by the reactive species directly, or as a secondary interaction in an oxidative relay. Briefly, irreversible (carbonylation, nitration) oxidative modifications affect a variety of amino acids including cysteine (Cys), threonine and tyrosine (Ahmad et al 2017;Cai and Yan 2013;Xie et al 2018). In contrast, reversible amino acid oxidation involves modification of the thiol group (-SH) of Cys protein residues that are first modified to sulfenic acid (-SOH) (Cai and Yan 2013).…”

“…A specialised form of disulphide bond formation, glutathionylation (R-S-S-G) arises as a mixed disulphide bond formation between a target protein Cys residue and the non-enzymatic antioxidant, glutathione (GSH) (Cai and Yan 2013). Further oxidation of -SOH results in an irreversible Cys oxidation by the formation of sulfinic (-SO 2 H) and sulfonic (-SO 3 H) acids (Ahmad et al 2017;Cai and Yan 2013;Murray and Van Eyk 2012). Autophagy regulation by ROS is linked to the reversible oxidative Cys modification of (a) transcription factors (TFs) that regulate expression of proteins involved in the autophagy process, (b) upstream regulators of autophagy initiation, (c) autophagy proteins themselves and (d) receptors that mediate autophagy substrate selectivity (Filomeni et al 2015;Montagna et al 2016;Sedlackova et al 2020).…”

Oxidation of phenylalanyl-tRNA synthetase positively regulates translational quality control

“…DNA, RNA, and proteins can be affected by oxygen radicals independently; therefore, all steps of translating the genetic code are susceptible to oxidative stress (8)(9)(10)(11)(12). Amino acid oxidation can cause changes to proteins that allow different interactions with the environment and altered activity (13). Oxidative stress causes diverse effects on aaRSs in various organisms.…”

Beyond the A‐layer: adsorption of lipopolysaccharides and characterization of bacteriophage‐insensitive mutants of Aeromonas salmonicida subsp. salmonicida

“…The mutation resulted in the modification of cysteine at position 219 to a phenylalanine. Cysteines are known to be sometime implicated in the formation of disulfide bridges permitting the stabilization of the native conformation of a protein (Ahmad et al , ). The impact of the replacement of a cysteine by a phenylalanine (hydrophobic amino acid) in ASA_1998 remains to be elucidated.…”