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Deamidation of asparagine residues: direct hydrolysis versus succinimide-mediated deamidation mechanisms

Saron Catak UGent, Gerald Monard, Viktorya Aviyente and Manuel F. Ruiz-Lopez (2009) JOURNAL OF PHYSICAL CHEMISTRY A. 113(6). p.1111-1120
abstract
Quantum chemical calculations are reported to provide new insights on plausible mechanisms leading to the deamidation of asparagine residues in proteins and peptides. Direct hydrolysis to aspartic acid and several succinimide-mediated mechanisms have been described. The catalytic effect of water molecules has been explicitly analyzed. Calculations have been carried out at the density functional level (B3LYP/6-31+G**). Comparisons of free energy profiles show that the most favorable reaction mechanism goes through formation of a succinimide intermediate and involves tautomerization of the asparagine amide to the corresponding imidic acid as the initial reaction step. Another striking result is that direct water-assisted hydrolysis is competitive with the succinimide-mediated deamidation routes even in the absence of acid or base catalysis. The rate-determining step for the formation of the succinimide intermediate is cyclization, regardless of the mechanism. The rate-determining step for the complete deamidation is the hydrolysis of the succinimide intermediate. These results allow clarification of some well-known facts, such as the isolation of succinimide or the absence of iso-Asp among the reaction products observed in some experiments.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
RATES, RIBONUCLEASE, PEPTIDES, ISOMERIZATION, 3-DIMENSIONAL STRUCTURE, GLUTAMINYL, AB-INITIO, NONENZYMATIC DEAMIDATION, ASPARTIC-ACID, PENTAPEPTIDES
journal title
JOURNAL OF PHYSICAL CHEMISTRY A
J. Phys. Chem. A
volume
113
issue
6
pages
1111 - 1120
publisher
AMER CHEMICAL SOC
place of publication
Washington, USA
Web of Science type
Article
Web of Science id
000263134900022
JCR category
PHYSICS, ATOMIC, MOLECULAR & CHEMICAL
JCR impact factor
2.899 (2009)
JCR rank
8/33 (2009)
JCR quartile
1 (2009)
ISSN
1089-5639
DOI
10.1021/jp808597v
language
English
UGent publication?
no
classification
A1
id
594662
handle
http://hdl.handle.net/1854/LU-594662
date created
2009-04-16 11:50:32
date last changed
2017-01-02 09:57:01
@article{594662,
  abstract     = {Quantum chemical calculations are reported to provide new insights on plausible mechanisms leading to the deamidation of asparagine residues in proteins and peptides. Direct hydrolysis to aspartic acid and several succinimide-mediated mechanisms have been described. The catalytic effect of water molecules has been explicitly analyzed. Calculations have been carried out at the density functional level (B3LYP/6-31+G**). Comparisons of free energy profiles show that the most favorable reaction mechanism goes through formation of a succinimide intermediate and involves tautomerization of the asparagine amide to the corresponding imidic acid as the initial reaction step. Another striking result is that direct water-assisted hydrolysis is competitive with the succinimide-mediated deamidation routes even in the absence of acid or base catalysis. The rate-determining step for the formation of the succinimide intermediate is cyclization, regardless of the mechanism. The rate-determining step for the complete deamidation is the hydrolysis of the succinimide intermediate. These results allow clarification of some well-known facts, such as the isolation of succinimide or the absence of iso-Asp among the reaction products observed in some experiments.},
  author       = {Catak, Saron and Monard, Gerald and Aviyente, Viktorya and Ruiz-Lopez, Manuel F.},
  issn         = {1089-5639},
  journal      = {JOURNAL OF PHYSICAL CHEMISTRY A},
  keyword      = {RATES,RIBONUCLEASE,PEPTIDES,ISOMERIZATION,3-DIMENSIONAL STRUCTURE,GLUTAMINYL,AB-INITIO,NONENZYMATIC DEAMIDATION,ASPARTIC-ACID,PENTAPEPTIDES},
  language     = {eng},
  number       = {6},
  pages        = {1111--1120},
  publisher    = {AMER CHEMICAL SOC},
  title        = {Deamidation of asparagine residues: direct hydrolysis versus succinimide-mediated deamidation mechanisms},
  url          = {http://dx.doi.org/10.1021/jp808597v},
  volume       = {113},
  year         = {2009},
}

Chicago
Catak, Saron, Gerald Monard, Viktorya Aviyente, and Manuel F. Ruiz-Lopez. 2009. “Deamidation of Asparagine Residues: Direct Hydrolysis Versus Succinimide-mediated Deamidation Mechanisms.” Journal of Physical Chemistry A 113 (6): 1111–1120.
APA
Catak, S., Monard, G., Aviyente, V., & Ruiz-Lopez, M. F. (2009). Deamidation of asparagine residues: direct hydrolysis versus succinimide-mediated deamidation mechanisms. JOURNAL OF PHYSICAL CHEMISTRY A, 113(6), 1111–1120.
Vancouver
1.
Catak S, Monard G, Aviyente V, Ruiz-Lopez MF. Deamidation of asparagine residues: direct hydrolysis versus succinimide-mediated deamidation mechanisms. JOURNAL OF PHYSICAL CHEMISTRY A. Washington, USA: AMER CHEMICAL SOC; 2009;113(6):1111–20.
MLA
Catak, Saron, Gerald Monard, Viktorya Aviyente, et al. “Deamidation of Asparagine Residues: Direct Hydrolysis Versus Succinimide-mediated Deamidation Mechanisms.” JOURNAL OF PHYSICAL CHEMISTRY A 113.6 (2009): 1111–1120. Print.