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 language | English |
|---|---|
| Pages (from-to) | 1405-1413 |
| Number of pages | 9 |
| Journal | Journal of Computational Chemistry |
| Volume | 30 |
| Issue number | 9 |
| DOIs | |
| State | Published - Jul 15 2009 |
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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
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. / Barman, Arghya; Taves, Woody; Prabhakar, Rajeev.
In: Journal of Computational Chemistry, Vol. 30, No. 9, 15.07.2009, p. 1405-1413.Research output: Contribution to journal › Article
}
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 -