Biological significance of nitric oxide-mediated protein modifications

Abstract

Nitric oxide (NO), despite an apparently simple diatomic structure, has a wide variety of functions in both physiology and pathology and within every major organ system. It has become an increasingly important scientific challenge to decipher how this wide range of activity is achieved. To this end a number of investigators have begun to explore how NO-mediated posttranslational modifications of proteins may represent mechanisms of cellular signaling. These modifications include: 1). binding to metal centers; 2). nitrosylation of thiol and amine groups; 3). nitration of tyrosine, tryptophan, amine, carboxylic acid, and phenylalanine groups; and 4). oxidation of thiols (both cysteine and methionine residues) and tyrosine. However, two particular modifications have recently received much attention, nitrosylation of thiols to produce S-nitrosothiol and nitration of tyrosine residues to produce nitrotyrosine. It is the purpose of this review to examine the possibility that these modifications may play a role in NO-mediated signaling.

When is Mass Spectrometry Combined with Affinity Approaches Essential? A Case Study of Tyrosine Nitration in Proteins

“…The possible role of sequence and structural environment for nitration has been discussed by several authors [11,23,33,36,40,[46][47][48]. Ischiropoulos et al [47] have pointed out the importance of the protein structure for regulation of nitration sites, which is consistent with our results on surface accessibilities in the nitration of eosinophil proteins (Figure 4). A specific sequence prerequisite for nitration, analogous to the specific sequence for tyrosine phosphorylation by tyrosine kinases [49], has not yet been established from the present studies, and more detailed work employing tyrosine-nitrated model peptides is required to obtain more conclusive results.…”

“…Changes of sensor-phase signals were fitted with the programs OriginPro 7.5 (OriginLab Corp., Northampton, MA, USA) and FitMaster (SAWInstruments, Bonn, Germany). Determination of antibody/ protein association kinetics was performed by extracting the data from the sensor signals using the monomolecular growth model [47]. Determinations of dissociation constants was performed by plotting the pseudo first-order kinetic constants for two independent channels verss concentration, and applying linear regression for K D =k off k on -1 for nitration sites, comprising cationic amino acids in the vicinity of nitrated tyrosine residues (Table 2) [46].…”

“…Determinations of dissociation constants was performed by plotting the pseudo first-order kinetic constants for two independent channels verss concentration, and applying linear regression for K D =k off k on -1 for nitration sites, comprising cationic amino acids in the vicinity of nitrated tyrosine residues (Table 2) [46]. The possible role of sequence and structural environment for nitration has been discussed by several authors [11,23,33,36,40,[46][47][48]. Ischiropoulos et al [47] have pointed out the importance of the protein structure for regulation of nitration sites, which is consistent with our results on surface accessibilities in the nitration of eosinophil proteins (Figure 4).…”

Identification of S-nitrosylation motifs by site-specific mapping of the S -nitrosocysteine proteome in human vascular smooth muscle cells

“…Also, the crystal structures for these proteins have not been determined. Therefore, the presence of common motifs for some but not all proteins identified from CysNO and PAPANO treatments suggests that protein S-nitrosocysteine formation derived from the nitric oxide radical donor include both secondary reactions of nitric oxide to generate transnitrosating species as well as other potential chemistries (8,9).…”

“…The formation of protein S-nitrosocysteine requires the removal of a single electron, i.e., the conversion of the nitrogen in nitric oxide from an oxidation state of 2 to 3. Several distinct pathways could satisfy the formation of protein S-nitrosocysteine adducts in biological systems, such as autooxidation of nitric oxide forming higher oxides of nitrogen, radical recombination of thiyl radical with nitric oxide, catalysis by metal centers, the direct reaction of nitric oxide with a reduced cysteine followed by electron abstraction, and transnitrosation reactions carried out by S-nitrosoglutathione, other small molecular mass S-nitrosothiols, and more recently, S-nitrosocysteine-containing proteins (8)(9)(10).…”