Nonspecificity of Binding of γ-Secretase Modulators to the Amyloid Precursor Protein

被引：37

作者：

Beel, Andrew J. ^{[1
,2
]}

Barrett, Paul ^{[1
,2
]}

Schnier, Paul D. ^{[3
]}

Hitchcock, Stephen A. ^{[3
]}

Bagal, Dhanashri ^{[3
]}

Sanders, Charles R. ^{[1
,2
]}

Jordan, John B. ^{[3
]}

机构：

[1] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Struct Biol Ctr, Nashville, TN 37232 USA

[3] Amgen Inc, Dept Mol Struct, Thousand Oaks, CA 91320 USA

来源：

BIOCHEMISTRY | 2009年 / 48卷 / 50期

基金：

美国国家卫生研究院;

关键词：

NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ALZHEIMERS-DISEASE; POTASSIUM CHANNEL; PEPTIDE; HYPOTHESIS; INHIBITORS; COMMON; KCNE1;

D O I：

10.1021/bi901839d

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 previous work and that binding of GSMs to these C99 aggregates is also of a nonspecific nature.

引用

页码：11837 / 11839

页数：3

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