Aspartate-bond isomerization affects the major conformations of synthetic peptides

G. I. Szendrei, H. Fabian, H. H. Mantsch, Sándor Lovas, O. Nyeki, I. Schon, L. Otvos

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The aspartic acid bond changes to an β-aspartate bond frequently as a side-reaction during peptide synthesis and often as a post-translational modification of proteins. The formation of β-aspartate bonds is reported to play a major role not only in protein metabolism, activation and deactivation, but also in pathological processes such as deposition of the neuritic plaques of Alzheimer's disease. Recently, we reported how conformational changes following the aspartic-acid-bond isomerization may help the selective aggregation and retention of the amyloid β peptide in affected brains (Fabian et al., 1994). In the current study we used circular dichroism, Fourier-transform infrared spectroscopy, and molecular modeling to characterize the general effect of the β-aspartate-bond formation on the conformation of five sets of synthetic model peptides. Each of the non-modified, parent peptides has one of the major secondary structures as the dominant spectroscopically determined conformation: a type I β turn, a type II β turn, short segments of α or 310 helices, or extended β strands. We found that both types of turn structures are stabilized by the aspartic acid-bond isomerization. The isomerization at a terminal position did not affect the helix propensity, but placing it in mid-chain broke both the helix and the β-pleated sheet with the formation of reverse turns. The alteration of the geometry of the lowest energy reverse turn was also supported by molecular dynamics calculations. The tendency of the aspartic acid-bond isomerization to stabilize turns is very similar to the effect of incorporating sugars into synthetic peptides and suggests a common feature of these post-translational modifications in defining the secondary structure of protein fragments.

Original languageEnglish
Pages (from-to)917-924
Number of pages8
JournalEuropean Journal of Biochemistry
Volume226
Issue number3
DOIs
StatePublished - 1994

Fingerprint

Isomerization
Aspartic Acid
Conformations
Peptides
Post Translational Protein Processing
Secondary Protein Structure
Proteins
Molecular modeling
Amyloid Plaques
Dichroism
Fourier Transform Infrared Spectroscopy
Pathologic Processes
Molecular Dynamics Simulation
Circular Dichroism
Amyloid
Metabolism
Sugars
Molecular dynamics
Brain
Alzheimer Disease

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Aspartate-bond isomerization affects the major conformations of synthetic peptides. / Szendrei, G. I.; Fabian, H.; Mantsch, H. H.; Lovas, Sándor; Nyeki, O.; Schon, I.; Otvos, L.

In: European Journal of Biochemistry, Vol. 226, No. 3, 1994, p. 917-924.

Research output: Contribution to journalArticle

Szendrei, G. I. ; Fabian, H. ; Mantsch, H. H. ; Lovas, Sándor ; Nyeki, O. ; Schon, I. ; Otvos, L. / Aspartate-bond isomerization affects the major conformations of synthetic peptides. In: European Journal of Biochemistry. 1994 ; Vol. 226, No. 3. pp. 917-924.
@article{984d8fd2306d4787b6685f0d34d29309,
title = "Aspartate-bond isomerization affects the major conformations of synthetic peptides",
abstract = "The aspartic acid bond changes to an β-aspartate bond frequently as a side-reaction during peptide synthesis and often as a post-translational modification of proteins. The formation of β-aspartate bonds is reported to play a major role not only in protein metabolism, activation and deactivation, but also in pathological processes such as deposition of the neuritic plaques of Alzheimer's disease. Recently, we reported how conformational changes following the aspartic-acid-bond isomerization may help the selective aggregation and retention of the amyloid β peptide in affected brains (Fabian et al., 1994). In the current study we used circular dichroism, Fourier-transform infrared spectroscopy, and molecular modeling to characterize the general effect of the β-aspartate-bond formation on the conformation of five sets of synthetic model peptides. Each of the non-modified, parent peptides has one of the major secondary structures as the dominant spectroscopically determined conformation: a type I β turn, a type II β turn, short segments of α or 310 helices, or extended β strands. We found that both types of turn structures are stabilized by the aspartic acid-bond isomerization. The isomerization at a terminal position did not affect the helix propensity, but placing it in mid-chain broke both the helix and the β-pleated sheet with the formation of reverse turns. The alteration of the geometry of the lowest energy reverse turn was also supported by molecular dynamics calculations. The tendency of the aspartic acid-bond isomerization to stabilize turns is very similar to the effect of incorporating sugars into synthetic peptides and suggests a common feature of these post-translational modifications in defining the secondary structure of protein fragments.",
author = "Szendrei, {G. I.} and H. Fabian and Mantsch, {H. H.} and S{\'a}ndor Lovas and O. Nyeki and I. Schon and L. Otvos",
year = "1994",
doi = "10.1111/j.1432-1033.1994.t01-1-00917.x",
language = "English",
volume = "226",
pages = "917--924",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Aspartate-bond isomerization affects the major conformations of synthetic peptides

AU - Szendrei, G. I.

AU - Fabian, H.

AU - Mantsch, H. H.

AU - Lovas, Sándor

AU - Nyeki, O.

AU - Schon, I.

AU - Otvos, L.

PY - 1994

Y1 - 1994

N2 - The aspartic acid bond changes to an β-aspartate bond frequently as a side-reaction during peptide synthesis and often as a post-translational modification of proteins. The formation of β-aspartate bonds is reported to play a major role not only in protein metabolism, activation and deactivation, but also in pathological processes such as deposition of the neuritic plaques of Alzheimer's disease. Recently, we reported how conformational changes following the aspartic-acid-bond isomerization may help the selective aggregation and retention of the amyloid β peptide in affected brains (Fabian et al., 1994). In the current study we used circular dichroism, Fourier-transform infrared spectroscopy, and molecular modeling to characterize the general effect of the β-aspartate-bond formation on the conformation of five sets of synthetic model peptides. Each of the non-modified, parent peptides has one of the major secondary structures as the dominant spectroscopically determined conformation: a type I β turn, a type II β turn, short segments of α or 310 helices, or extended β strands. We found that both types of turn structures are stabilized by the aspartic acid-bond isomerization. The isomerization at a terminal position did not affect the helix propensity, but placing it in mid-chain broke both the helix and the β-pleated sheet with the formation of reverse turns. The alteration of the geometry of the lowest energy reverse turn was also supported by molecular dynamics calculations. The tendency of the aspartic acid-bond isomerization to stabilize turns is very similar to the effect of incorporating sugars into synthetic peptides and suggests a common feature of these post-translational modifications in defining the secondary structure of protein fragments.

AB - The aspartic acid bond changes to an β-aspartate bond frequently as a side-reaction during peptide synthesis and often as a post-translational modification of proteins. The formation of β-aspartate bonds is reported to play a major role not only in protein metabolism, activation and deactivation, but also in pathological processes such as deposition of the neuritic plaques of Alzheimer's disease. Recently, we reported how conformational changes following the aspartic-acid-bond isomerization may help the selective aggregation and retention of the amyloid β peptide in affected brains (Fabian et al., 1994). In the current study we used circular dichroism, Fourier-transform infrared spectroscopy, and molecular modeling to characterize the general effect of the β-aspartate-bond formation on the conformation of five sets of synthetic model peptides. Each of the non-modified, parent peptides has one of the major secondary structures as the dominant spectroscopically determined conformation: a type I β turn, a type II β turn, short segments of α or 310 helices, or extended β strands. We found that both types of turn structures are stabilized by the aspartic acid-bond isomerization. The isomerization at a terminal position did not affect the helix propensity, but placing it in mid-chain broke both the helix and the β-pleated sheet with the formation of reverse turns. The alteration of the geometry of the lowest energy reverse turn was also supported by molecular dynamics calculations. The tendency of the aspartic acid-bond isomerization to stabilize turns is very similar to the effect of incorporating sugars into synthetic peptides and suggests a common feature of these post-translational modifications in defining the secondary structure of protein fragments.

UR - http://www.scopus.com/inward/record.url?scp=0028556901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028556901&partnerID=8YFLogxK

U2 - 10.1111/j.1432-1033.1994.t01-1-00917.x

DO - 10.1111/j.1432-1033.1994.t01-1-00917.x

M3 - Article

VL - 226

SP - 917

EP - 924

JO - FEBS Journal

JF - FEBS Journal

SN - 1742-464X

IS - 3

ER -