γ-分泌酶调节剂与淀粉样前体蛋白结合的非特异性。
Nonspecificity of binding of gamma-secretase modulators to the amyloid precursor protein.
机构信息
Department of Biochemistry and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232-8725, USA.
出版信息
Biochemistry. 2009 Dec 22;48(50):11837-9. doi: 10.1021/bi901839d.
Abstract
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.
摘要
有证据表明，某些γ-分泌酶调节剂（GSMs）靶向γ-分泌酶的底物淀粉样前体蛋白的 99 个残基 C 端结构域（C99），而不是蛋白酶复合物本身[Kukar，T.L.等人。（2008）自然 453,925-929]。在这里，NMR 结果表明这些 GSMs 与 LMPG 胶束中单分散 C99 没有特异性结合。此外，结果表明，在之前工作的一些关键实验中，C99 很可能已经聚集，并且 GSMs 与这些 C99 聚集体的结合也具有非特异性。
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2
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3
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4
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Cell Mol Life Sci. 2008 May;65(9):1311-34. doi: 10.1007/s00018-008-7462-2.
5
Preparation, functional characterization, and NMR studies of human KCNE1, a voltage-gated potassium channel accessory subunit associated with deafness and long QT syndrome.
Biochemistry. 2007 Oct 16;46(41):11459-72. doi: 10.1021/bi700705j. Epub 2007 Sep 25.
6
Insensitivity to Abeta42-lowering nonsteroidal anti-inflammatory drugs and gamma-secretase inhibitors is common among aggressive presenilin-1 mutations.
J Biol Chem. 2007 Aug 24;282(34):24504-13. doi: 10.1074/jbc.M700618200. Epub 2007 Jun 15.
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10
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