NR ARJS
AU Requena,J.R.; Dimitrova,M.N.; Legname,G.; Teijeira,S.; Prusiner,S.B.; Levine,R.L.
TI Oxidation of methionine residues in the prion protein by hydrogen peroxide
QU Archives of Biochemistry and Biophysics 2004 Dec 15; 432(2): 188-95
PT journal article
AB 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.
MH Animals; Binding Sites; Hamsters; Hydrogen Peroxide/*chemistry; Mesocricetus; Methionine/*chemistry; Multiprotein Complexes/chemistry; Oxidation-Reduction; Peptide Fragments/*chemistry; Prions/*chemistry; Protein Binding; Protein Conformation; Protein Structure, Secondary; Recombinant Proteins/chemistry; Research Support, Non-U.S. Gov't; Structure-Activity Relationship
AD Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. requenaj@usc.es
SP englisch
PO USA