Mechanistic Study on Electron Capture Dissociation of the Oligosaccharide-Mg2+ Complex

  • Yiqun Huang
  • Yi Pu
  • Xiang Yu
  • Catherine E. Costello
  • Cheng Lin
Research Article

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.

Keywords

Electron capture dissociation (ECD) Oligosaccharides Fragmentation mechanism FT-ICR Molecular dynamics simulation Density functional theory Tandem mass spectrometry 

Supplementary material

13361_2014_921_MOESM1_ESM.docx (429 kb)
ESM 1(DOCX 428 kb)

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Copyright information

© American Society for Mass Spectrometry 2014

Authors and Affiliations

  • Yiqun Huang
    • 1
    • 2
  • Yi Pu
    • 1
    • 3
  • Xiang Yu
    • 1
    • 2
  • Catherine E. Costello
    • 1
    • 2
    • 3
  • Cheng Lin
    • 1
    • 2
  1. 1.Mass Spectrometry ResourceBoston University School of MedicineBostonUSA
  2. 2.Department of BiochemistryBoston University School of MedicineBostonUSA
  3. 3.Department of ChemistryBoston UniversityBostonUSA

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