Statistical and mechanistic approaches to understanding the gas-phase fragmentation behavior of methionine sulfoxide containing peptides
Details
Publication Year 2004-07, Volume 3, Issue #4, Page 751-759
Journal Title
JOURNAL OF PROTEOME RESEARCH
Publication Type
Journal Article
Abstract
Recently, we carried out a statistical analysis of a 'tryptic' peptide tandem mass spectrometry database in order to identify sequence-dependent patterns for the gas-phase fragmentation behavior of protonated peptide ions, and to improve the models for peptide fragmentation currently incorporated into peptide sequencing and database search algorithms [Kapp, E. A., Schutz, F., Reid, G. E., Eddes, J. S., Moritz, R. L., O'Hair, R. A. J., Speed, T. P. and Simpson, R. J. Anal. Chem. 2003, 75, 6251-6264.]. Here, we have reexamined this database in order to determine the effect of a common post-translational or process induced modification, methionine oxidation, on the appearance and relative abundances of the product ions formed by low energy collision induced dissociation of peptide ions containing this modification. The results from this study indicate that the structurally diagnostic neutral loss of methane sulfenic acid (CH3SOH, 64Da) from the side chain of methionine sulfoxide residues is the dominant fragmentation process for methionine sulfoxide containing peptide ions under conditions of low proton mobility, i.e., when ionizing proton(s) are sequestered at strongly basic amino acids such as arginine, lysine or histidine. The product ion abundances resulting from this neutral loss were found to be approximately 2-fold greater than those resulting from the cleavage C-terminal to aspartic acid, which has previously been shown to be enhanced under the same conditions. In close agreement with these statistical trends, experimental and theoretical studies, employing synthetic "tryptic" peptides and model methionine sulfoxide containing peptide ions, have determined that the mechanism for enhanced methionine sulfoxide side chain cleavage proceeds primarily via a 'charge remote' process. However, the mechanism for dissociation of the side chain for these ions was observed to change as a function of proton mobility. Finally, the transition state barrier for the charge remote side chain cleavage mechanism is predicted to be energetically more favorable than that for charge remote cleavage C-terminal to aspartic acid.
Publisher
AMER CHEMICAL SOC
Keywords
TANDEM MASS-SPECTRA; AMINO-ACID-SEQUENCES; PROTONATED PEPTIDES; PROTEIN DATABASE; METASTABLE DECOMPOSITION; INDUCED DISSOCIATION; NEIGHBORING GROUP; TRYPTIC PEPTIDES; ION CHEMISTRY; AB-INITIO
Publisher's Version
https://doi.org/10.1021/pr0499646
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2004-07-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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