Nonspecificity of Binding of γ-Secretase Modulators to the Amyloid Precursor Protein
Nonspecificity of Binding of γ-Secretase Modulators to the Amyloid Precursor Protein
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DOI：
10.1021/bi901839d
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发表时间：
2009-12-22
期刊：
影响因子：
2.9
通讯作者：
Jordan, John B.
中科院分区：
文献类型：
--
作者：
Beel, Andrew J.;Barrett, Paul;Jordan, John B.
某些γ-分泌酶调节剂（GSM）靶向淀粉样前体蛋白的99个残基的C-末端结构域（C99）（γ-分泌酶的底物）而不是蛋白酶复合物本身的证据已经被提出[Kukar，T. L.，等人（2008）Nature 453，925-929]。在这里，NMR结果表明，这些GSM的LMPG胶束中的单分散C99的特异性结合的缺乏，此外，结果表明，C99可能已经聚集在一些以前的工作的关键实验和GSM的这些C99聚集体的结合也是非特异性的。
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.