Open AccessCharacterization of novel oxidation products of cysteine in an active site motif peptide of PTP1B
Author(s) -
Vivekananda Shetty,
Thomas A. Neubert
Publication year - 2009
Publication title -
journal of the american society for mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.961
H-Index - 127
eISSN - 1879-1123
pISSN - 1044-0305
DOI - 10.1016/j.jasms.2009.04.011
Subject(s) - chemistry , sulfenic acid , cysteine , tandem mass spectrometry , mass spectrometry , peptide , protein tyrosine phosphatase , combinatorial chemistry , tyrosine , chromatography , biochemistry , enzyme
We investigated the formation of hydroxyl radical (OH(*)) and H(2)O(2) mediated oxidation products of a synthetic peptide, HCSAGIGRS, which is an active site sequence motif of protein tyrosine phosphatase 1B (PTP1B). We determined that a novel cysteine sulfinamide HC[S(O)N]SAGIGRS is produced in the oxidation reaction by Fenton reagents (Fe(+2)/H(2)O(2)) as well as by H(2)O(2). These products were characterized by tandem mass spectrometry experiments on both singly and doubly charged precursor ions. MS(3) experiments using an ion trap instrument as well as LC-MS/MS experiments using a quadrupole time-of-flight (Q-TOF) instrument demonstrated that HC[S(O)N]SAGIGRS is not a water loss product of cysteine sulfinic acid [HC(SO(2)H)SAGIGRS]. We also obtained data from tandem mass spectrometry experiments that provided evidence for the existence of stable cysteine sulfenic acid [HC(SOH)SAGIGRS] in solution. A mechanism for the formation of the cysteine sulfinamide product is proposed based on the above experimental results. The preparation and identification of cysteine sulfinamide in this study may provide insight into the mechanism of both OH(*) and H(2)O(2) induced oxidation reactions of protein tyrosine phosphatases.