Hydrogen rearrangement to and from radical z fragments in electron capture dissociation of peptides

Mikhail M Savitski, Frank Kjeldsen, Michael L Nielsen, Roman A Zubarev

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Hydrogen rearrangement is an important process in radical chemistry. A high degree of H. rearrangement to and from z. ionic fragments (combined occurrence frequency 47% compared with that of z.) is confirmed in analysis of 15,000 tandem mass spectra of tryptic peptides obtained with electron capture dissociation (ECD), including previously unreported double H. losses. Consistent with the radical character of H. abstraction, the residue determining the formation rate of z' = z. + H. species is found to be the N-terminal residue in z. species. The size of the complementary c(m)' fragment turned out to be another important factor, with z' species dominating over z. ions for m <or = 6. The H. atom was found to be abstracted from the side chains as well as from alpha-carbon groups of residues composing the c' species, with Gln and His in the c' fragment promoting H. donation and Asp and Ala opposing it. Ab initio calculations of formation energies of .A radicals (A is an amino acid) confirmed that the main driving force for H. abstraction by z. is the process exothermicity. No valid correlation was found between the NC(alpha) bond strength and the frequency of this bond cleavage, indicating that other factors than thermochemistry are responsible for directing the site of ECD cleavage. Understanding hydrogen attachment to and loss from ECD fragments should facilitate automatic interpretation ECD mass spectra in protein identification and characterization, including de novo sequencing.
OriginalsprogEngelsk
TidsskriftJournal of The American Society for Mass Spectrometry
Vol/bind18
Udgave nummer1
Sider (fra-til)113-20
Antal sider8
ISSN1044-0305
DOI
StatusUdgivet - 1. jan. 2007

Fingeraftryk

Hydrogen
Electrons
Peptides
Thermochemistry
Carbon
Ions
Amino Acids
Atoms
Proteins

Citer dette

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title = "Hydrogen rearrangement to and from radical z fragments in electron capture dissociation of peptides",
abstract = "Hydrogen rearrangement is an important process in radical chemistry. A high degree of H. rearrangement to and from z. ionic fragments (combined occurrence frequency 47{\%} compared with that of z.) is confirmed in analysis of 15,000 tandem mass spectra of tryptic peptides obtained with electron capture dissociation (ECD), including previously unreported double H. losses. Consistent with the radical character of H. abstraction, the residue determining the formation rate of z' = z. + H. species is found to be the N-terminal residue in z. species. The size of the complementary c(m)' fragment turned out to be another important factor, with z' species dominating over z. ions for m <or = 6. The H. atom was found to be abstracted from the side chains as well as from alpha-carbon groups of residues composing the c' species, with Gln and His in the c' fragment promoting H. donation and Asp and Ala opposing it. Ab initio calculations of formation energies of .A radicals (A is an amino acid) confirmed that the main driving force for H. abstraction by z. is the process exothermicity. No valid correlation was found between the NC(alpha) bond strength and the frequency of this bond cleavage, indicating that other factors than thermochemistry are responsible for directing the site of ECD cleavage. Understanding hydrogen attachment to and loss from ECD fragments should facilitate automatic interpretation ECD mass spectra in protein identification and characterization, including de novo sequencing.",
keywords = "Cell Line, Escherichia coli, Humans, Hydrogen, Mass Spectrometry, Peptides, Proteomics, Tandem Mass Spectrometry",
author = "Savitski, {Mikhail M} and Frank Kjeldsen and Nielsen, {Michael L} and Zubarev, {Roman A}",
year = "2007",
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Hydrogen rearrangement to and from radical z fragments in electron capture dissociation of peptides. / Savitski, Mikhail M; Kjeldsen, Frank; Nielsen, Michael L; Zubarev, Roman A.

I: Journal of The American Society for Mass Spectrometry, Bind 18, Nr. 1, 01.01.2007, s. 113-20.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Hydrogen rearrangement to and from radical z fragments in electron capture dissociation of peptides

AU - Savitski, Mikhail M

AU - Kjeldsen, Frank

AU - Nielsen, Michael L

AU - Zubarev, Roman A

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Hydrogen rearrangement is an important process in radical chemistry. A high degree of H. rearrangement to and from z. ionic fragments (combined occurrence frequency 47% compared with that of z.) is confirmed in analysis of 15,000 tandem mass spectra of tryptic peptides obtained with electron capture dissociation (ECD), including previously unreported double H. losses. Consistent with the radical character of H. abstraction, the residue determining the formation rate of z' = z. + H. species is found to be the N-terminal residue in z. species. The size of the complementary c(m)' fragment turned out to be another important factor, with z' species dominating over z. ions for m <or = 6. The H. atom was found to be abstracted from the side chains as well as from alpha-carbon groups of residues composing the c' species, with Gln and His in the c' fragment promoting H. donation and Asp and Ala opposing it. Ab initio calculations of formation energies of .A radicals (A is an amino acid) confirmed that the main driving force for H. abstraction by z. is the process exothermicity. No valid correlation was found between the NC(alpha) bond strength and the frequency of this bond cleavage, indicating that other factors than thermochemistry are responsible for directing the site of ECD cleavage. Understanding hydrogen attachment to and loss from ECD fragments should facilitate automatic interpretation ECD mass spectra in protein identification and characterization, including de novo sequencing.

AB - Hydrogen rearrangement is an important process in radical chemistry. A high degree of H. rearrangement to and from z. ionic fragments (combined occurrence frequency 47% compared with that of z.) is confirmed in analysis of 15,000 tandem mass spectra of tryptic peptides obtained with electron capture dissociation (ECD), including previously unreported double H. losses. Consistent with the radical character of H. abstraction, the residue determining the formation rate of z' = z. + H. species is found to be the N-terminal residue in z. species. The size of the complementary c(m)' fragment turned out to be another important factor, with z' species dominating over z. ions for m <or = 6. The H. atom was found to be abstracted from the side chains as well as from alpha-carbon groups of residues composing the c' species, with Gln and His in the c' fragment promoting H. donation and Asp and Ala opposing it. Ab initio calculations of formation energies of .A radicals (A is an amino acid) confirmed that the main driving force for H. abstraction by z. is the process exothermicity. No valid correlation was found between the NC(alpha) bond strength and the frequency of this bond cleavage, indicating that other factors than thermochemistry are responsible for directing the site of ECD cleavage. Understanding hydrogen attachment to and loss from ECD fragments should facilitate automatic interpretation ECD mass spectra in protein identification and characterization, including de novo sequencing.

KW - Cell Line

KW - Escherichia coli

KW - Humans

KW - Hydrogen

KW - Mass Spectrometry

KW - Peptides

KW - Proteomics

KW - Tandem Mass Spectrometry

U2 - 10.1016/j.jasms.2006.09.008

DO - 10.1016/j.jasms.2006.09.008

M3 - Journal article

C2 - 17059886

VL - 18

SP - 113

EP - 120

JO - Journal of The American Society for Mass Spectrometry

JF - Journal of The American Society for Mass Spectrometry

SN - 1044-0305

IS - 1

ER -