title: Investigation of local primary structure effects on peroxynitrite-mediated tyrosine nitration using targeted mass spectrometry.
abstract: Protein-tyrosine nitration (PTN) is a posttranslational modification resulting from cellular nitrosative stress that has been implicated in a wide variety of disease states. Determination of factors that influence selectivity of PTN remains a major challenge due to several issues including low biological levels of PTN, proximity of target sites on a single analyte, and analytical limitations for site-specific quantification of the nitration modification. We report a systematic approach that addresses relevant contributing factors to PTN with particular focus on determining the effect of changing proximal amino acid side chain structure on tyrosine nitration yield. A trend was observed in which nitration yield tends to be greater when the tyrosine residue is surrounded by basic and/or uncharged polar residues compared to nitration levels observed when hydrophobic and acidic residues are proximal to the tyrosine residue. Moreover, an electric dipole effect was observed where a higher degree of charge asymmetry surrounding the tyrosine residue correlates with an increased tyrosine nitration yield in certain cases. The reported data are expected to facilitate site-specific prediction and validation of PTN, especially in cases of potential target residues that share a similar solvent exposure environment and contain elements of known higher-order structure.
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: Kent W
authors.initials: KW
authors.lastname: Seeley
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Stevens
mesh_terms: D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D030421:Peroxynitrous Acid / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014443:Tyrosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; D011506:Proteins; D030421:Peroxynitrous Acid; D012710:Serum Albumin, Bovine; C002744:3-nitrotyrosine; D014443:Tyrosine