Tyrosine phosphorylation/dephosphorylation regulates peroxynitrite-mediated peptide nitration.
Proteins are targets of reactive nitrogen species such as peroxynitrite and nitrogen dioxide. Among the various amino acids in proteins, tyrosine and tryptophan residues are especially susceptible to attack by reactive nitrogen species. On the other hand, protein tyrosine phosphorylation has gained much attention in respect to cellular regulatory events and signal transduction. Peroxynitrite-mediated nitration of peptide YPPPPPW and phosphopeptide pYPPPPPW were studied at pH 7.4. The predominant nitrated products were separated and identified by reverse phase high performance liquid chromatography coupled with electrospray ionization mass spectrometry (LC-MS). The nitration sites were established by tandem electrospray ionization-mass spectrometry (LC-MS/MS). A regulatory effect of tyrosine phosphorylation/dephosphorylation on peptide nitration was observed. YPPPPPW was predominantly nitrated at tyrosine residue while pYPPPPPW was nitrated at tryptophan one. Our results can help in understanding the biochemical significance of the relationship of tyrosine phosphorylation and nitration in proteins.
Key Laboratory of Bioorganic Phosphorous Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, PR China.
Wei-Qun
WQ
Shi
Hui
H
Cai
Dian-Dou
DD
Xu
Xiao-Yang
XY
Su
Peng
P
Lei
Yu-Fen
YF
Zhao
Yan-Mei
YM
Li
D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D009566:Nitrates / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D010766:Phosphorylation; D053719:Tandem Mass Spectrometry; D014443:Tyrosine / Q000737:chemistry* / Q000378:metabolism
D009566:Nitrates; D009842:Oligopeptides; D010446:Peptide Fragments; C526878:YPPPPPW peptide; D030421:Peroxynitrous Acid; D014443:Tyrosine