1ba6
From Proteopedia
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SOLUTION STRUCTURE OF THE METHIONINE-OXIDIZED AMYLOID BETA-PEPTIDE (1-40). DOES OXIDATION AFFECT CONFORMATIONAL SWITCHING? NMR, 10 STRUCTURES
Contents |
Overview
The solution structure of Abeta(1-40)Met(O), the methionine-oxidized form, of amyloid beta-peptide Abeta(1-40), has been investigated by CD and NMR, spectroscopy. Oxidation of Met35 may have implications in the aetiology of, Alzheimer's disease. Circular dichroism experiments showed that whereas, Abeta(1-40) and Abeta(1-40)Met(O) both adopt essentially random coil, structures in water (pH 4) at micromolar concentrations, the former, aggregates within several days while the latter is stable for at least 7, days under these conditions. This remarkable difference led us to, determine the solution structure of Abeta(1-40)Met(O) using 1H NMR, spectroscopy. In a water-SDS micelle medium needed to solubilize both, peptides at the millimolar concentrations required to measure NMR spectra, chemical shift and NOE data for Abeta(1-40)Met(O) strongly suggest the, presence of a helical region between residues 16 and 24. This is supported, by slow H-D exchange of amide protons in this region and by structure, calculations using simulated annealing with the program XPLOR. The, remainder of the structure is relatively disordered. Our previously, reported NMR data for Abeta(1-40) in the same solvent shows that helices, are present over residues 15-24 (helix 1) and 28-36 (helix 2). Oxidation, of Met35 thus causes a local and selective disruption of helix 2. In, addition to this helix-coil rearrangement in aqueous micelles, the CD data, show that oxidation inhibits a coil-to-beta-sheet transition in water., These significant structural rearrangements in the C-terminal region of, Abeta may be important clues to the chemistry and biology of Abeta(1-40), and Abeta(1-42).
Disease
Known diseases associated with this structure: Alzheimer disease-1, APP-related OMIM:[104760], Amyloidosis, cerebroarterial, Dutch type OMIM:[104760], Amyloidosis, cerebroarterial, Iowa type OMIM:[104760], Blood group, P system OMIM:[607922]
About this Structure
1BA6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure of methionine-oxidized amyloid beta-peptide (1-40). Does oxidation affect conformational switching?, Watson AA, Fairlie DP, Craik DJ, Biochemistry. 1998 Sep 15;37(37):12700-6. PMID:9737846
Page seeded by OCA on Mon Nov 12 16:07:34 2007
