Transition metal ions: charge carriers that mediate the electron capture dissociation pathways of peptides.

Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Journal of the American Society for Mass Spectrometry (Impact Factor: 3.59). 09/2011; 22(12):2232-45. DOI: 10.1007/s13361-011-0246-1
Source: PubMed

ABSTRACT Electron capture dissociation (ECD) of model peptides adducted with first row divalent transition metal ions, including Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+), were investigated. Model peptides with general sequence of ZGGGXGGGZ were used as probes to unveil the ECD mechanism of metalated peptides, where X is either V or W; and Z is either R or N. Peptides metalated with different divalent transition metal ions were found to generate different ECD tandem mass spectra. ECD spectra of peptides metalated by Mn(2+) and Zn(2+) were similar to those generated by ECD of peptides adducted with alkaline earth metal ions. Series of c-/z-type fragment ions with and without metal ions were observed. ECD of Fe(2+), Co(2+), and Ni(2+) adducted peptides yielded abundant metalated a-/y-type fragment ions; whereas ECD of Cu(2+) adducted peptides generated predominantly metalated b-/y-type fragment ions. From the present experimental results, it was postulated that electronic configuration of metal ions is an important factor in determining the ECD behavior of the metalated peptides. Due presumably to the stability of the electronic configuration, metal ions with fully-filled (i.e., Zn(2+)) and half filled (i.e., Mn(2+)) d-orbitals might not capture the incoming electron. Dissociation of the metal ions adducted peptides would proceed through the usual ECD channel(s) via "hot-hydrogen" or "superbase" intermediates, to form series of c-/z(•)- fragments. For other transition metal ions studied, reduction of the metal ions might occur preferentially. The energy liberated by the metal ion reduction would provide enough internal energy to generate the "slow-heating" type of fragment ions, i.e., metalated a-/y- fragments and metalated b-/y- fragments.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The use of metal salts in electrospray ionization (ESI) of peptides increases the charge state of peptide ions, facilitating electron transfer dissociation (ETD) in tandem mass spectrometry. In the present study, K(+) and Ca(2+) were used as charge carriers to form multiply-charged metal-peptide complexes. ETD of the potassium- or calcium-peptide complex was initiated by transfer of an electron to a proton remote from the metal cation, and a c'-z• fragment complex, in which the c' and z• fragments were linked together via a metal cation coordinating with several amino acid residues, was formed. The presence of a metal cation in the precursor for ETD increased the lifetime of the c'-z• fragment complex, eventually generating c• and z' fragments through inter-fragment hydrogen migration. The degree of hydrogen migration was dependent on the location of the metal cation in the metal-peptide complex, but was not reconciled with conformation of the precursor ion obtained by molecular mechanics simulation. In contrast, the location of the metal cation in the intermediate suggested by the ETD spectrum was in agreement with the conformation of "proton-removed" precursors, indicating that the charge reduction of precursor ions by ETD induces conformational rearrangement during the fragmentation process.
    Journal of the American Society for Mass Spectrometry 03/2014; 25(6). · 3.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Electron capture dissociation (ECD) has shown great potential in structural characterization of glycans. However, our current understanding of the glycan ECD process is inadequate for accurate interpretation of the complex glycan ECD spectra. Here, we present the first comprehensive theoretical investigation on the ECD fragmentation behavior of metal-adducted glycans, using the cellobiose-Mg2+ complex as the model system. Molecular dynamics simulation was carried out to determine the typical glycan-Mg2+ binding patterns and the lowest-energy conformer identified was used as the initial geometry for density functional theory-based theoretical modeling. It was found that the electron is preferentially captured by Mg2+ and the resultant Mg+• can abstract a hydroxyl group from the glycan moiety to form a carbon radical. Subsequent radical migration and α-cleavage(s) result in the formation of a variety of product ions. The proposed hydroxyl abstraction mechanism correlates well with the major features in the ECD spectrum of the Mg2+-adducted cellohexaose. The mechanism presented here also predicts the presence of secondary, radical-induced fragmentation pathways. These secondary fragment ions could be misinterpreted, leading to erroneous structural determination. The present study highlights an urgent need for continuing investigation of the glycan ECD mechanism, which is imperative for successful development of bioinformatics tools that can take advantage of the rich structural information provided by ECD of metal-adducted glycans.
    Journal of the American Society for Mass Spectrometry 05/2014; 25(8). · 3.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: With electrospray ionization from aqueous solutions, trivalent metal ions readily adduct to small peptides resulting in formation of predominantly (peptide + M(T) - H)(2+), where M(T) = La, Tm, Lu, Sm, Ho, Yb, Pm, Tb, or Eu, for peptides with molecular weights below ~1000 Da, and predominantly (peptide + M(T))(3+) for larger peptides. ECD of (peptide + M(T) - H)(2+) results in extensive fragmentation from which nearly complete sequence information can be obtained, even for peptides for which only singly protonated ions are formed in the absence of the metal ions. ECD of these doubly charged complexes containing M(T) results in significantly higher electron capture efficiency and sequence coverage than peptide-divalent metal ion complexes that have the same net charge. Formation of salt-bridge structures in which the metal ion coordinates to a carboxylate group are favored even for (peptide + M(T))(3+). ECD of these latter complexes for large peptides results in electron capture by the protonation site located remotely from the metal ion and predominantly c/z fragments for all metals, except Eu(3+), which undergoes a one electron reduction and only loss of small neutral molecules and b/y fragments are formed. These results indicate that solvation of the metal ion in these complexes is extensive, which results in the electrochemical properties of these metal ions being similar in both the peptide environment and in bulk water.
    Journal of the American Society for Mass Spectrometry 01/2013; · 3.59 Impact Factor

Full-text (2 Sources)

Available from
May 20, 2014