| Title | Oxidation of methionine residues in the prion protein by hydrogen peroxide. | | Author(s) | Requena JR, Dimitrova MN, Legname G, Teijeira S, Prusiner SB, Levine RL | | Institution | Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. requenaj@usc.es | | Source | Arch Biochem Biophys 2004 Dec 15; 432(2):188-95. | | MeSH | Animals
Binding Sites
Cricetinae
Hydrogen Peroxide
Mesocricetus
Methionine
Multiprotein Complexes
Oxidation-Reduction
Peptide Fragments
Prions
Protein Binding
Protein Conformation
Protein Structure, Secondary
Recombinant Proteins
Research Support, Non-U.S. Gov't
Structure-Activity Relationship
| | Abstract | Reaction of H(2)O(2) with the recombinant SHa(29-231) prion protein resulted in rapid oxidation of multiple methionine residues. Susceptibility to oxidation of individual residues, assessed by mass spectrometry after digestion with CNBr and lysC, was in general a function of solvent exposure. Met 109 and Met 112, situated in the highly flexible amino terminus, and key residues of the toxic peptide PrP (106-126), showed the greatest susceptibility. Met 129, a residue located in a polymorphic position in human PrP and modulating risk of prion disease, was also easily oxidized, as was Met 134. The structural effect of H(2)O(2)-induced methionine oxidation on PrP was studied by CD spectroscopy. As opposed to copper catalyzed oxidation, which results in extensive aggregation of PrP, this reaction led only to a modest increase in beta-sheet structure. The high number of solvent exposed methionine residues in PrP suggests their possible role as protective endogenous antioxidants. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 15542057 |
|
