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DFT-based elucidation of asparagine deamidation in peptides

Saron Catak UGent, Bart De Sterck UGent, Gerald Monard, Manuel F Ruiz-López, Viktorya Aviyente, Michel Waroquier UGent and Veronique Van Speybroeck UGent (2010) Quantum Chemistry in Belgium, 9th edition, Abstracts.
abstract
Asparagine (Asn) residues spontaneously – yet non-enzymatically – deamidate to form aspartate under physiological conditions, causing time-dependent changes in the conformation of proteins, limiting their lifetime [1]. Deamidation has been associated with aging, development and protein turnover. The ‘molecular clocks’ hypothesis [2], suggests that deamidation is a biological molecular timing mechanism that could be set to any desired time interval by genetic control of the protein structure and the immediate environment of the Asn residue. The fact that deamidation occurs over a wide range of biologically relevant time intervals suggests that different mechanisms may be at play. To date deamidation is believed to occur over a succinimide-mediated pathway [3]. Concerted and stepwise pathways leading to the succinimide intermediate were previously explored with the inclusion of explicit water molecules [4]; a novel route leading to the succinimide intermediate via tautomerization of the Asn side chain amide functionality was proposed [5]. The feasibility of the tautomerization route was further explored with QM metadynamics calculations. The current study also introduces a new ‘competing’ route for deamidation of asparagine residues. The aim is to comparatively analyze the feasibility of this new mechanism against the traditional succinimide route. These results will help identify the lowest energy pathway for asparagine deamidation and will serve as a stepping stone for calculations on deamidation in proteins.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
published
subject
in
Quantum Chemistry in Belgium, 9th edition, Abstracts
publisher
Université Catholique de Louvain (UCL)
place of publication
Louvain-la-Neuve, Belgium
conference name
9th edition of Quantum Chemistry in Belgium (QCB-9)
conference location
Louvain-la-Neuve, Belgium
conference start
2010-01-26
conference end
2010-01-26
language
English
UGent publication?
yes
classification
C3
copyright statement
I have transferred the copyright for this publication to the publisher
id
1162519
handle
http://hdl.handle.net/1854/LU-1162519
alternative location
http://www.uclouvain.be/307896.html
date created
2011-02-21 14:30:28
date last changed
2011-05-18 11:32:28
@inproceedings{1162519,
  abstract     = {Asparagine (Asn) residues spontaneously -- yet non-enzymatically -- deamidate to form aspartate under physiological conditions, causing time-dependent changes in the conformation of proteins, limiting their lifetime [1]. Deamidation has been associated with aging, development and protein turnover. The {\textquoteleft}molecular clocks{\textquoteright} hypothesis [2], suggests that deamidation is a biological molecular timing mechanism that could be set to any desired time interval by genetic control of the protein structure and the immediate environment of the Asn residue. The fact that deamidation occurs over a wide range of biologically relevant time intervals suggests that different mechanisms may be at play. To date deamidation is believed to occur over a succinimide-mediated pathway [3]. Concerted and stepwise pathways leading to the succinimide intermediate were previously explored with the inclusion of explicit water molecules [4]; a novel route leading to the succinimide intermediate via tautomerization of the Asn side chain amide functionality was proposed [5]. The feasibility of the tautomerization route was further explored with QM metadynamics calculations. The current study also introduces a new {\textquoteleft}competing{\textquoteright} route for deamidation of asparagine residues. The aim is to comparatively analyze the feasibility of this new mechanism against the traditional succinimide route. These results will help identify the lowest energy pathway for asparagine deamidation and will serve as a stepping stone for calculations on deamidation in proteins.},
  author       = {Catak, Saron and De Sterck, Bart and Monard, Gerald and Ruiz-L{\'o}pez, Manuel F and Aviyente, Viktorya and Waroquier, Michel and Van Speybroeck, Veronique},
  booktitle    = {Quantum Chemistry in Belgium, 9th edition, Abstracts},
  language     = {eng},
  location     = {Louvain-la-Neuve, Belgium},
  publisher    = {Universit{\'e} Catholique de Louvain (UCL)},
  title        = {DFT-based elucidation of asparagine deamidation in peptides},
  url          = {http://www.uclouvain.be/307896.html},
  year         = {2010},
}

Chicago
Catak, Saron, Bart De Sterck, Gerald Monard, Manuel F Ruiz-López, Viktorya Aviyente, Michel Waroquier, and Veronique Van Speybroeck. 2010. “DFT-based Elucidation of Asparagine Deamidation in Peptides.” In Quantum Chemistry in Belgium, 9th Edition, Abstracts. Louvain-la-Neuve, Belgium: Université Catholique de Louvain (UCL).
APA
Catak, S., De Sterck, B., Monard, G., Ruiz-López, M. F., Aviyente, V., Waroquier, M., & Van Speybroeck, V. (2010). DFT-based elucidation of asparagine deamidation in peptides. Quantum Chemistry in Belgium, 9th edition, Abstracts. Presented at the 9th edition of Quantum Chemistry in Belgium (QCB-9), Louvain-la-Neuve, Belgium: Université Catholique de Louvain (UCL).
Vancouver
1.
Catak S, De Sterck B, Monard G, Ruiz-López MF, Aviyente V, Waroquier M, et al. DFT-based elucidation of asparagine deamidation in peptides. Quantum Chemistry in Belgium, 9th edition, Abstracts. Louvain-la-Neuve, Belgium: Université Catholique de Louvain (UCL); 2010.
MLA
Catak, Saron, Bart De Sterck, Gerald Monard, et al. “DFT-based Elucidation of Asparagine Deamidation in Peptides.” Quantum Chemistry in Belgium, 9th Edition, Abstracts. Louvain-la-Neuve, Belgium: Université Catholique de Louvain (UCL), 2010. Print.