Nonspecificity of binding of gamma-secretase modulators to the amyloid precursor protein.
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ABSTRACT:
SUBMITTER: Beel AJ
PROVIDER: S-EPMC2794937 | biostudies-literature | 2009 Dec
REPOSITORIES: biostudies-literature
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Nonspecificity of binding of gamma-secretase modulators to the amyloid precursor protein.
Beel Andrew J AJ Barrett Paul P Schnier Paul D PD Hitchcock Stephen A SA Bagal Dhanashri D Sanders Charles R CR Jordan John B JB
Biochemistry 20091201 50
Evidence that certain gamma-secretase modulators (GSMs) target the 99-residue C-terminal domain (C99) of the amyloid precursor protein, a substrate of gamma-secretase, but not the protease complex itself has been presented [Kukar, T. L., et al. (2008) Nature 453, 925-929]. Here, NMR results demonstrate a lack of specific binding of these GSMs to monodisperse C99 in LMPG micelles. In addition, results indicate that C99 was likely to have been aggregated in some of the key experiments of the previ ...[more]
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