Article

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: 3.19). 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.

Download full-text

Full-text

Available from: Yi Man Eva Fung, Jul 07, 2015
0 Followers
 · 
235 Views
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Addition of 1.0 mM LaCl(3) to aqueous ammonium acetate solutions containing proteins in their folded native forms can result in a significant increase in the molecular ion charging obtained with electrospray ionization as a result of cation adduction. In combination with m-nitrobenzyl alcohol, molecular ion charge states that are greater than the number of basic sites in the protein can be produced from these native solutions, even for lysozyme, which is conformationally constrained by four intramolecular disulfide bonds. Circular dichroism spectroscopy indicates that the conformation of ubiquitin is not measurably affected with up to 1.0 M LaCl(3), but ion mobility data indicate that the high charge states that are formed when 1.0 mM LaCl(3) is present are more unfolded than the low charge states formed without this reagent. These and other results indicate that the increased charging is a result of La(3+) preferentially adducting onto compact or more native-like conformers during ESI and the gas-phase ions subsequently unfolding as a result of increased Coulomb repulsion. Electron capture dissociation of these high charge-state ions formed from these native solutions results in comparable sequence coverage to that obtained for ions formed from denaturing solutions without supercharging reagents, making this method a potentially powerful tool for obtaining structural information in native mass spectrometry.
    Journal of the American Society for Mass Spectrometry 09/2012; 23(11):1885-95. DOI:10.1007/s13361-012-0463-2 · 3.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The reactions of Sc(+) ((3) D, (1) D) and Fe(+) ((6) D, (4)  F) with acetone have been investigated in both high- and low-spin states using density functional theory. Our calculations have indicated that oxidation of Sc(+) by acetone can take place by (1) metal-mediated H migration, (2) direct methyl-H shift and/or (3) C = O insertion. The most energetically favorable pathway is metal-mediated H migration followed by intramolecular ScO(+) rotation and dissociation. For the deethanization of acetone mediated by Fe(+) , the reaction occurs on either the quartet or sextet surfaces through five elementary steps, i.e. encounter complexation, C-C bond activation, methyl migration, C-C coupling and non-reactive dissociation. The rate-determining step along the quartet-state potential-energy surface (PES) is similar to that in the case of Ni(+) ((2)  F, 3d(9) ), namely the methyl-migration step. For the sextet-state PES, however, the energy barrier for methyl migration is lower than that for C-C bond activation, and the rate-determining step is C-C coupling. In general, the low-spin-state pathways are lower in energy than the high-spin-state pathways; therefore, the reaction pathways for the oxidation of Sc(+) and the Fe(+) -mediated deethanization of acetone mostly involve the low-spin states. Copyright © 2012 John Wiley & Sons, Ltd.
    Journal of Mass Spectrometry 11/2012; 47(11):1518-25. DOI:10.1002/jms.3099 · 2.71 Impact Factor