Insights into the mechanism of methionine oxidation catalyzed by metal (Cu 2+, Zn 2+, and Fe 3+) - Amyloid beta (Aβ) peptide complexes: A computational study

Arghya Barman, Woody Taves, Rajeev Prabhakar

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

In this DFT study, a mechanism of the oxidation of methionine (Met) amino acid residue catalyzed by the metal (Cu 2+, Zn 2+, and Fe 3+) bound amyloid beta (Aβ) peptide has been proposed. Based on experimental information, two different mechanisms: (1) stepwise and (2) concerted mechanisms for this important process have been investigated. The B3LYP calculations suggest that in the stepwise mechanism, the two separate pathways leading to the same sulfoxide product [Met(O)] go through prohibitively high barriers of 27.3 and 35.1 kcal/mol, therefore it is ruled out. In the concerted mechanism, the Cu 2+ -Aβ complex has been found to be the most efficient catalyst with the computed barrier of 14.3 kcal/mol. The substitutions of Cu 2+ by Zn 2+ and Fe 3+ increase barriers to 19.6 and 16.9 kcal/mol, respectively and make the reaction thermodynamically less favorable. It was also found that, in comparison with the cysteine (Cys) residue, Met is more susceptible toward oxidation. Its substitution with Cys slightly increased the barrier to 15.8 kcal/mol for the Cu 2+ -Aβ complex.

Original languageEnglish
Pages (from-to)1405-1413
Number of pages9
JournalJournal of Computational Chemistry
Volume30
Issue number9
DOIs
StatePublished - Jul 15 2009

Fingerprint

Amyloid
Peptides
Oxidation
Methionine
sulfoxide
Substitution reactions
Metals
Cysteine
Discrete Fourier transforms
Amino acids
Substitution
Catalysts
Amino Acids
Catalyst
Pathway

Keywords

  • Amyloid beta (Aβ)-peptide
  • Met oxidation
  • Metal-Aβ complex
  • Reaction mechanism
  • Reactive oxygen species

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics

Cite this

@article{12592079ad2c4b33a17c0d82c0afda36,
title = "Insights into the mechanism of methionine oxidation catalyzed by metal (Cu 2+, Zn 2+, and Fe 3+) - Amyloid beta (Aβ) peptide complexes: A computational study",
abstract = "In this DFT study, a mechanism of the oxidation of methionine (Met) amino acid residue catalyzed by the metal (Cu 2+, Zn 2+, and Fe 3+) bound amyloid beta (Aβ) peptide has been proposed. Based on experimental information, two different mechanisms: (1) stepwise and (2) concerted mechanisms for this important process have been investigated. The B3LYP calculations suggest that in the stepwise mechanism, the two separate pathways leading to the same sulfoxide product [Met(O)] go through prohibitively high barriers of 27.3 and 35.1 kcal/mol, therefore it is ruled out. In the concerted mechanism, the Cu 2+ -Aβ complex has been found to be the most efficient catalyst with the computed barrier of 14.3 kcal/mol. The substitutions of Cu 2+ by Zn 2+ and Fe 3+ increase barriers to 19.6 and 16.9 kcal/mol, respectively and make the reaction thermodynamically less favorable. It was also found that, in comparison with the cysteine (Cys) residue, Met is more susceptible toward oxidation. Its substitution with Cys slightly increased the barrier to 15.8 kcal/mol for the Cu 2+ -Aβ complex.",
keywords = "Amyloid beta (Aβ)-peptide, Met oxidation, Metal-Aβ complex, Reaction mechanism, Reactive oxygen species",
author = "Arghya Barman and Woody Taves and Rajeev Prabhakar",
year = "2009",
month = "7",
day = "15",
doi = "10.1002/jcc.21167",
language = "English",
volume = "30",
pages = "1405--1413",
journal = "Journal of Computational Chemistry",
issn = "0192-8651",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

TY - JOUR

T1 - Insights into the mechanism of methionine oxidation catalyzed by metal (Cu 2+, Zn 2+, and Fe 3+) - Amyloid beta (Aβ) peptide complexes

T2 - A computational study

AU - Barman, Arghya

AU - Taves, Woody

AU - Prabhakar, Rajeev

PY - 2009/7/15

Y1 - 2009/7/15

N2 - In this DFT study, a mechanism of the oxidation of methionine (Met) amino acid residue catalyzed by the metal (Cu 2+, Zn 2+, and Fe 3+) bound amyloid beta (Aβ) peptide has been proposed. Based on experimental information, two different mechanisms: (1) stepwise and (2) concerted mechanisms for this important process have been investigated. The B3LYP calculations suggest that in the stepwise mechanism, the two separate pathways leading to the same sulfoxide product [Met(O)] go through prohibitively high barriers of 27.3 and 35.1 kcal/mol, therefore it is ruled out. In the concerted mechanism, the Cu 2+ -Aβ complex has been found to be the most efficient catalyst with the computed barrier of 14.3 kcal/mol. The substitutions of Cu 2+ by Zn 2+ and Fe 3+ increase barriers to 19.6 and 16.9 kcal/mol, respectively and make the reaction thermodynamically less favorable. It was also found that, in comparison with the cysteine (Cys) residue, Met is more susceptible toward oxidation. Its substitution with Cys slightly increased the barrier to 15.8 kcal/mol for the Cu 2+ -Aβ complex.

AB - In this DFT study, a mechanism of the oxidation of methionine (Met) amino acid residue catalyzed by the metal (Cu 2+, Zn 2+, and Fe 3+) bound amyloid beta (Aβ) peptide has been proposed. Based on experimental information, two different mechanisms: (1) stepwise and (2) concerted mechanisms for this important process have been investigated. The B3LYP calculations suggest that in the stepwise mechanism, the two separate pathways leading to the same sulfoxide product [Met(O)] go through prohibitively high barriers of 27.3 and 35.1 kcal/mol, therefore it is ruled out. In the concerted mechanism, the Cu 2+ -Aβ complex has been found to be the most efficient catalyst with the computed barrier of 14.3 kcal/mol. The substitutions of Cu 2+ by Zn 2+ and Fe 3+ increase barriers to 19.6 and 16.9 kcal/mol, respectively and make the reaction thermodynamically less favorable. It was also found that, in comparison with the cysteine (Cys) residue, Met is more susceptible toward oxidation. Its substitution with Cys slightly increased the barrier to 15.8 kcal/mol for the Cu 2+ -Aβ complex.

KW - Amyloid beta (Aβ)-peptide

KW - Met oxidation

KW - Metal-Aβ complex

KW - Reaction mechanism

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=67650113074&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650113074&partnerID=8YFLogxK

U2 - 10.1002/jcc.21167

DO - 10.1002/jcc.21167

M3 - Article

C2 - 19037857

AN - SCOPUS:67650113074

VL - 30

SP - 1405

EP - 1413

JO - Journal of Computational Chemistry

JF - Journal of Computational Chemistry

SN - 0192-8651

IS - 9

ER -