Calmodulin Methionine Residues are Targets For One-Electron Oxidation by Hydroxyl Radicals: Formation of S therefore N three-electron bonded Radical Complexes
The one-electron (1e) oxidation of organic sulfides and methionine (Met) constitutes an important reaction mechanism in vivo.1,2 Evidence for a Cu(II)-catalyzed oxidation of Met35 in the Alzheimer's disease -amyloid peptide was obtained,3 and, based on theoretical studies, Met radical cations were proposed as intermediates.4 In the structure of -amyloid peptide, the formation of Met radical cations appears to be facilitated by a preexisting close sulfur-oxygen (S-O) interaction between the Met35 sulfur and the carbonyl oxygen of the peptide bond C-terminal to Ile31.5 Substitution of Ile31 with Pro31 abolishes this S-O interaction,5 significantly reducing the ability of -amyloid to reduce Cu(II), and converts the neurotoxic wild-type -amyloid into a non-toxic peptide.6 The preexisting S-O bond characterized for wild-type -amyloid suggests that electron transfer from Met35 to Cu(II) is supported through stabilization of the Met radical cation by the electron-rich carbonyl oxygen, generating an SO-bonded7 sulfide radical cation (Scheme 1, reaction 1).5
- Research Organization:
- Pacific Northwest National Lab., Richland, WA (US)
- Sponsoring Organization:
- US Department of Energy (US)
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 15016359
- Report Number(s):
- PNWD-SA-6574; TRN: US200513%%170
- Journal Information:
- Chemical Communications, Vol. 5; Other Information: PBD: 1 Feb 2005
- Country of Publication:
- United States
- Language:
- English
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