Abstract
Electron capture dissociation (ECD) and collision-induced dissociation (CID), the two complementary fragmentation techniques, are demonstrated to be effective in the detection and localization of the methionine sulfoxide [Met(O)] residues in peptides using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. The presence of Met(O) can be easily recognized in the low-energy CID spectrum showing the characteristic loss of methanesulfenic acid (CH3SOH, 64 Da) from the side chain of Met(O). The position of Met(O) can then be localized by ECD which is capable of providing extensive peptide backbone fragmentation without detaching the labile Met(O) side chain. We studied CID and ECD of several Met(O)-containing peptides that included the 44-residue human growth hormone-releasing factor (GRF) and the human atrial natriuretic peptide (ANP). The distinction and complementarity of the two fragmentation techniques were particularly remarkable in their effects on ANP, a disulfide bond-containing peptide. While the predominant fragmentation pathway in CID of ANP was the loss of CH3SOH (64 Da) from the molecular ion, ECD of ANP resulted in many sequence-informative products, including those from cleavages within the disulfide-bonded cyclic structure, to allow for the direct localization of Met(O) without the typical procedures for disulfide bond reduction followed by -SH alkylation.
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Berlett, B. S.; Stadtman, E. R. Protein Oxidation in Aging, Disease, and Oxidative Stress. J. Biol. Chem. 1997, 272(33), 20313–20316.
Stadtman, E. R.; Levine, R. L. Protein Oxidation. Annu. N. Y. Acad. Sci. 2000, 899, 191–208.
Stadtman, E. R.; Berlett, B. S. Reactive Oxygen-Mediated Protein Oxidation in Aging and Disease. Chem. Res. Toxicol. 1997, 10(5), 485–494.
Vogt, W. Oxidation of Methionyl Residues in Proteins: Tools, Targets, and Reversal. Free Rad. Biol. Med. 1995, 18, 93–105.
Gao, J.; Yin, D. H.; Yao, Y.; Sun, H.; Qin, Z.; Schöneich, C.; Williams, T. D.; Squier, T. C. Loss of Conformational Stability in Calmodulin Upon Methionine Oxidation. Biophys. J. 1998, 74, 1115–1134.
Gao, J.; Yin, D.; Yao, Y.; Williams, T. D.; Squier, T. C. Progressive Decline in the Ability of Calmodulin Isolated from Aged Brain to Activate the Plasma Membrane Ca-ATPase. Biochemistry. 1998, 37, 9536–9548.
Palmblad, M.; Westlind-Danielsson, A.; Bergquist, J. Oxidation of Methionine 35 Attenuates Formation of Amyloid β-Peptide 1–40 Oligomers. J. Biol. Chem. 2002, 277, 19506–19510.
Kuo, Y.-M.; Webster, S.; Emmerling, M. R.; De Lima, N.; Roher, A. E. Irreversible Dimerization/Tetramerization and Post-translational Modifications Inhibit Proteolytic Degradation of A β Peptides of Alzheimer’s Disease. Biochim. Biophys. Acta. 1998, 1406, 291–296.
Hoshi, T.; Heinemann, S. H. Regulation of Cell Function by Methionine Oxidation and Reduction. J. Physiol. 2001, 531, 1–11.
Stadtman, E. R.; Moskovitz, J.; Berlett, B. S.; Levine, R. L. Cyclic Oxidation and Reduction of Protein Methionine Residues is an Important Antioxidant Mechanism. Mol. Cell. Biochem. 2002, 234/235, 3–9.
Ciorba, M. A.; Heinemann, S. H.; Weissbach, H.; Brot, N.; Hoshi, T. Modulation of Potassium Channel Function by Methionine Oxidation and Reduction. Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 9932–9937.
Marki, W.; Spiess, J.; Tache, Y.; Rivier, J. E. Total Solid-Phase Synthesis of Porcine Gut Gastrin Releasing Peptide (GRP), a Mammalian Bombesin. J. Am. Chem. Soc. 1981, 103, 3178–3185.
Asano, T.; Ashida, M. Transepithelially Transported Pro-Phenoloxidase in the Cuticle of the Silkworm. Bombyx mori. J. Biol. Chem. 2001, 276, 11113–11125.
Schey, K. L.; Finley, E. L. Identification of Peptide Oxidation by Tandem Mass Spectrometry. Acc. Chem. Res. 2000, 33, 299–306.
Lagerwerf, F. M.; van de Weert, M.; Heerma, W.; Haverkamp, J. Identification of Oxidized Methionine Peptides. Rapid Commun. Mass Spectrom. 1996, 10, 1905–1910.
Morand, K.; Talbo, G.; Mann, M. Oxidation of Peptides During Electrospray Ionization. Rapid Commun. Mass Spectrom. 1993, 7, 738–743.
Griffiths, S. W.; Cooney, C. L. Development of a Peptide Mapping Procedure to Identify and Quantify Methionine Oxidation in Recombinant Human α1-Antitrypsin. J. Chromatogr. A. 2002, 942, 133–143.
Jiang, X.; Smith, J. B.; Abraham, E. C. Identification of a MS-MS Fragment Diagnostic for Methionine Sulfoxide. J. Mass Spectrum. 1996, 31, 1309–1310.
Smith, J. B.; Jiang, X.; Abraham, E. C. Identification of Hydrogen Peroxide Oxidation Sites of αA- and αB-Crystallins. Free Rad. Res. 1997, 26, 103–111.
Steen, H.; Mann, M. Similarity Between Condensed Phase and Gas Phase Chemistry: Fragmentation of Peptides Containing Oxidized Cysteine Residues and Its Implications for Proteomics. J. Am. Soc. Mass Spectrom. 2001, 12, 228–232.
Kotiaho, T.; Eberlin, M. N.; Vainiotalo, P.; Kostianinen, R. Electrospray Mass and Tandem Mass Spectrometry Identification of Ozone Oxidation Products of Amino Acids and Small Peptides. J. Am. Soc. Mass Spectrom. 2000, 11, 526–535.
Zhu, H.; Hunter, T. C.; Pan, S.; Yau, P. M.; Bradbury, E. M.; Chen, X. Residue-Specific Mass Signatures for the Efficient Detection of Protein Modifications by Mass Spectrometry. Anal. Chem. 2002, 74, 1687–1694.
Hollemeyer, K.; Heinzle, E.; Tholey, A. Identification of Oxidized Methionine Residues in Peptides Containing Two Methionine Residues by Derivatization and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. Proteomics. 2002, 2, 1524–1531.
Busch, K. L.; Glish, G. L.; McLuckey, S. A. Mass Spectrometry/Mass Spectometry. Techniques and Applications of Tandem Mass Spectrometry (Monograph). VCH: New York, 1988.
Hunt, D. F.; Yates, J. R., III; Shabanowitz, J.; Winston, S.; Hauer, C. R. Protein Sequencing by Tandem Mass Spectrometry. Proc. Natl. Acad. Sci. U. S. A. 1986, 83, 6233–6237.
McLuckey, S. A.; Wells, J. M. Mass Analysis at the Advent of the 21st Century. Chem. Rev. 2001, 101, 571–606.
Senko, M. W.; Speir, J. P.; McLafferty, F. W. Collisional Activation of Large Multiply Charged Ions Using Fourier Transform Mass Spectrometry. Anal. Chem. 1994, 68, 2801–2808.
Turecek, F.; Drinkwater, D. E.; McLafferty, F. W. Gas-Phase Chemistry of CH3SOH, -CH +2 SHOH, CH3SO·, and ·CH2SOH by Neutralization-Reionization Mass Spectrometry. J. Am. Chem. Soc. 1989, 111, 7696–7701.
Zubarev, R. A.; Kelleher, N. L.; McLafferty, F. W. Electron Capture Dissociation of Multiply Charged Protein Cations. A Nonergodic Process. J. Am. Chem. Soc. 1998, 120, 3265–3266.
Zubarev, R. A.; Kruger, N. A.; Fridriksson, E. K.; Lewis, M. A.; Horn, D. M.; Carpenter, B. K.; McLafferty, F. W. Electron Capture Dissociation of Gaseous Multiply-Charged Proteins is Favored at Disulfide Bonds and Other Sites of High Hydrogen Atom Affinity. J. Am. Chem. Soc. 1999, 121, 2857–2862.
Zubarev, R. A.; Horn, D. A.; Fridriksson, E. K.; Kelleher, N. L.; Kruger, N. A.; Lewis, M. A.; Carpenter, B. K.; McLafferty, F. W. Electron Capture Dissociation for Structural Characterization of Multiply Charged Protein Cations. Anal. Chem. 2000, 72, 563–573.
Horn, D. M. Ge Ying; McLafferty, F. W. Activated Ion Electron Capture Dissociation for Mass Spectral Sequencing of Larger (42 kDa) Proteins. Anal. Chem. 2000, 72, 4778–4784.
McLafferty, F. W.; Horn, D. M.; Breuker, K.; Ge, Y.; Lewis, M. A.; Cerda, B.; Zubarev, R. A.; Carpenter, B. K. Electron Capture Dissociation of Gaseous Multiply Charged Ions by Fourier-Transform Ion Cyclotron Resonance. J. Am. Soc. Mass Spectrom. 2001, 12, 245–249.
Ge, Y.; Lawhorn, B. G.; El-Naggar, M.; Strauss, E.; Park, J.-H.; Begley, T. P.; McLafferty, F. W. Top Down Characterization of Larger Proteins (45 kDa) by Electron Capture Dissociation Mass Spectrometry. J. Am. Chem. Soc. 2002, 124, 672–678.
Sze, S. K.; Ge, Y.; Oh, H.-B.; McLafferty, F. W. Top-Down Mass Spectrometry of a 29-kDa Protein for Characterization of Any Posttranslational Modification to Within One Residue. Proc. Natl. Acad. Sci. U. S. A. 2002, 99(4), 1774–1779.
Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Electrospray Ionization for Mass Spectrometry of Large Biomolecules. Science. 1989, 246, 64–71.
Marshall, A. G.; Hendrickson, C. L.; Jackson, G. S. Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: A Primer. Mass Spectrom. Rev. 1998, 17, 1–36.
Little, D. P.; Speir, J. P.; Senko, M. W.; O’Connor, P. B.; McLafferty, F. W. Infrared Multiphoton Dissociation of Large Multiply Charged Ions for Biomolecule Sequencing. Anal. Chem. 1994, 66, 2809–2815.
Kelleher, N. L.; Zubarev, R. A.; Bush, K.; Furie, B.; Furie, B. C.; McLafferty, F. W.; Walsh, C. T. Localization of Labile Posttranslational Modifications by Electron Capture Dissociation: The Case of γ-Carboxyglutamic Acid. Anal. Chem. 1999, 71, 4250–4253.
Stenballe, A.; Jensen, O. N.; Olsen, J. V.; Haselmann, K. F.; Zubarev, R. A. Electron Capture Dissociation of Singly and Multiply Phosphorylated Peptides. Rapid Commun. Mass Spectrom. 2000, 14, 1793–1800.
Shi, S. D. H.; Hemling, M. E.; Carr, S. A.; Horn, D. M.; Lindh, I.; McLafferty, F. W. Phosphopeptide/Phosphoprotein Mapping by Electron Capture Dissociation Mass Spectrometry. Anal. Chem. 2001, 73, 19–22.
Mirgorodskaya, E.; Roepstorff, P.; Zubarev, R. A. Localization of O-Glycosylation Sites in Peptides by Electron Capture Dissociation in a Fourier Transform Mass Spectrometer. Anal. Chem. 1999, 71, 4431–4436.
Håkansson, K.; Cooper, H. J.; Emmett, M. R.; Costello, C. E.; Marshall, A. G.; Nilsson, C. L. Electron Capture Dissociation and Infrared Multiphoton Dissociation MS/MS of an N-Glycosylated Tryptic Peptide to Yield Complementary Sequence Information. Anal. Chem. 2001, 73, 4530–4536.
Guan, Z. Identification and Localization of the Fatty Acid Modification in Ghrelin by Electron Capture Dissociation. J. Am. Soc. Mass Spectrom. 2002, 13, 1941–1945.
Wilm, M. S.; Mann, M. Analytical Properties of the Nanoelectrospray Ion Source. Anal. Chem. 1996, 68, 1–8.
Winger, B. E.; Campana, J. E. Characterization of Combinatorial Peptide Libraries by Electrospray Ionization Fourier Transform Mass Spectrometry. Rapid Commun. Mass Spectrom. 1996, 10, 1811–1813.
Marshall, A. G.; Wang, T. C. L.; Ricca, T. L. Tailored Excitation for Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. J. Am. Chem. Soc. 1985, 107, 7893–7897.
Gauthier, J. W.; Trautman, T. R.; Jacobson, D. B. Sustained Off-Resonance Irradiation for Collision-Activated Dissociation Involving Fourier Transform Mass Spectrometry. Collision-Activated Dissociation Technique that Emulates Infrared Multiphoton Dissociation. Anal. Chim. Acta. 1991, 246, 211–225.
Cooper, H. J.; Hudgins, R. R.; Håkansson, K.; Marshall, A. G. Characterization of Amino Acid Side Chain Losses in Electron Capture Dissociation. J. Am. Soc. Mass Spectrom. 2002, 13, 241–249.
Loo, J. A.; Edmonds, C. G.; Udseth, H. R.; Smith, R. D. Effect of Reducing Disulfide-Containing Proteins on Electrospray Ionization Mass Spectra. Anal. Chem. 1990, 62, 693–698.
Axelsson, J.; Palmblad, M.; Håkansson, K.; Håakansson, P. Electron Capture Dissociation of Substance P Using a Commercially Available Fourier Transform Ion Cyclotron Resonance Mass Spectrometer. Rapid Commun. Mass Spectrom. 1999, 13, 474–477.
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Published online April 24, 2003
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Guan, Z., Yates, N.A. & Bakhtiar, R. Detection and characterization of methionine oxidation in peptides by collision-induced dissociation and electron capture dissociation. J Am Soc Mass Spectrom 14, 605–613 (2003). https://doi.org/10.1016/S1044-0305(03)00201-0
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DOI: https://doi.org/10.1016/S1044-0305(03)00201-0