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PDBsum entry 1ba6
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References listed in PDB file
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Key reference
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Title
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Solution structure of methionine-Oxidized amyloid beta-Peptide (1-40). Does oxidation affect conformational switching?
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Authors
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A.A.Watson,
D.P.Fairlie,
D.J.Craik.
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Ref.
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Biochemistry, 1998,
37,
12700-12706.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
88%.
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Abstract
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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).
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