Gas-phase structures of phosphopeptide ions: A difficult case

Tureček, František; Moss, Christopher L.; Pikalov, Ioannis; Pepin, Robert; Gulyuz, K.; Polfer, Nicolas C.; Bush, Matthew F.; Brown, Jeffery M.; Williams, Jonathan P.; Richardson, Keith

doi:10.1016/j.ijms.2013.06.021

Cited by 24 publications

(31 citation statements)

References 53 publications

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“…Figure S4 shows that there are differences among the isomers in absorbance at the laser main line (943 cm -1 ). When allowed for a red shift due to anharmonic corrections [41-43], the best overlap with the 10.6 μm laser line is obtained for 1a and 3b . Hence, it is plausible to assume that the dissociation pathway involving 3b receives additional photoexcitation to drive a kinetically preferred backbone cleavage.…”

Section: Resultsmentioning

confidence: 99%

Competitive hydrogen atom migrations accompanying cascade dissociations of peptide cation-radicals of the + type

Ledvina

Coon

Tureček

2015

International Journal of Mass Spectrometry

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We report a combined experimental and computational study of energy-resolved collision-induced dissociation (ER-CID) and time-resolved infrared multiphoton dissociation (TR-IRMPD) of z4 ions prepared by electron transfer dissociation of peptide (Ala-Ala-Asn-Ala-Arg + 2H)2+ ions. The z4 cation-radicals, •ANAR+, undergo competitive dissociations by backbone cleavage and loss of a CONH2 radical from the Asn side chain. The backbone cleavage proceeds by radical-assisted dissociation of the Asn Cα—CO bond, forming an x2 ion intermediate which rapidly dissociates by HNCO elimination to yield a stable z2 fragment ion, •AR+. The ER-CID and TR-IRMPD data were consistent with the consecutive nature of the backbone dissociation but showed different branching ratios for the two major fragmentations. The ER-CID data showed branching ratios 0.6-1.0 for the side-chain and backbone cleavages whereas the TR-IRMPD data showed an earlier onset for the latter dissociation. Computational analysis of the potential energy surface with density functional theory and ab initio calculations was carried out to provide structures and energies for the reactant ions as well as several intermediates, products, and transition states. Dissociation pathways for cis and trans amide conformers were distinguished and their energies were evaluated. The threshold dissociation energies for the backbone and side-chain dissociations were similar in accordance with the experimental ER-CID branching ratio. The TR-IRMPD data were interpreted by different absorbances of intermediates produced by hydrogen atom migrations along the dissociation pathways.

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Section: Resultsmentioning

confidence: 99%

Competitive hydrogen atom migrations accompanying cascade dissociations of peptide cation-radicals of the + type

Ledvina

Coon

Tureček

2015

International Journal of Mass Spectrometry

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“…Coupling IMS with fragmentation techniques such as photodissociation and electron transfer dissociation has been shown to improve phosphosite localization [36, 37]. Furthermore, IMS has been applied to understanding the mechanisms of phosphopeptide fragmentation [38–40]. …”

Section: Introductionmentioning

confidence: 99%

Examining the Influence of Phosphorylation on Peptide Ion Structure by Ion Mobility Spectrometry-Mass Spectrometry

Glover

Dilger

Acton

et al. 2016

J. Am. Soc. Mass Spectrom.

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Ion mobility spectrometry-mass spectrometry (IMS-MS) techniques are used to study the general effects of phosphorylation on peptide structure. Cross sections for a library of 66 singly phosphorylated peptide ions from 33 pairs of positional isomers, and unmodified analogues were measured. Intrinsic size parameters (ISPs) derived from these measurements yield calculated collision cross sections for 85% of these phosphopeptide sequences that are within ±2.5% of experimental values. The average ISP for the phosphoryl group (0.64 ± 0.05) suggests that in general this moiety forms intramolecular interactions with the neighboring residues and peptide backbone, resulting in relatively compact structures. We assess the capability of ion mobility to separate positional isomers (i.e., peptide sequences that differ only in the location of the modification) and find that more than half of the isomeric pairs have >1% difference in collision cross section. Phosphorylation is also found to influence populations of structures that differ in the cis/trans orientation of Xaa–Pro peptide bonds. Several sequences with phosphorylated Ser or Thr residues located N-terminally adjacent to Pro residues show fewer conformations compared to the unmodified sequences.

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“…The 21 → 24 proton transfer indicated by B3LYP and M062X calculations was nearly thermoneutral and did not alter the overall folding pattern of the ion. Note the very short distance between the COOH proton and the Lys ε-amine nitrogen in 24 (1.466 Å) and the similarly short N-H…OCO distance in 21 (1.519 Å), which are indicative of the fluxional nature and highly anharmonic N–H and O–H stretching vibrational modes in these tautomers [28, 76]. In contrast to 24 , moving a proton from the N -terminal ammonium to the Asp carboxylate did not result in a local energy minimum and the structure spontaneously collapsed back to 21 .…”

Section: Resultsmentioning

confidence: 99%

Toward a Rational Design of Highly Folded Peptide Cation Conformations. 3D Gas-Phase Ion Structures and Ion Mobility Characterization

Pepin

Laszlo

Marek

et al. 2016

J. Am. Soc. Mass Spectrom.

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Heptapeptide ions containing combinations of polar Lys, Arg, and Asp residues with non-polar Leu, Pro, Ala, and Gly residues were designed to study polar effects on gas-phase ion conformations. Doubly and triply charged ions were studied by ion mobility mass spectrometry and electron structure theory using correlated ab initio and density functional theory methods and found to exhibit tightly folded 3D structures in the gas phase. Manipulation of the basic residue positions in LKGPADR, LRGPADK, KLGPADR, and RLGPADK resulted in only minor changes in the ion collision cross sections in helium. Replacement of the Pro residue with Leu resulted in only marginally larger collision cross sections for the doubly and triply charged ions. Disruption of zwitterionic interactions in doubly charged ions was performed by converting the C-terminal and Asp carboxyl groups to methyl esters. This resulted in very minor changes in the collision cross sections of doubly charged ions and even slightly diminished collision cross sections in most triply charged ions. The experimental collision cross sections were related to those calculated for structures of lowest free energy ion conformers that were obtained by extensive search of the conformational space and fully optimized by density functional theory calculations. The predominant factors that affected ion structures and collision cross sections were due to attractive hydrogen bonding interactions and internal solvation of the charged groups that overcompensated their Coulomb repulsion. Structure features typically assigned to the Pro residue and zwitterionic COO-charged group interactions were only secondary in affecting the structures and collision cross sections of these gas-phase peptide ions.

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Gas-phase structures of phosphopeptide ions: A difficult case

Cited by 24 publications

References 53 publications

Competitive hydrogen atom migrations accompanying cascade dissociations of peptide cation-radicals of the + type

Competitive hydrogen atom migrations accompanying cascade dissociations of peptide cation-radicals of the + type

Examining the Influence of Phosphorylation on Peptide Ion Structure by Ion Mobility Spectrometry-Mass Spectrometry

Toward a Rational Design of Highly Folded Peptide Cation Conformations. 3D Gas-Phase Ion Structures and Ion Mobility Characterization

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