Department of Biochemistry and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee 37232-8725, USA.
Biochemistry. 2009 Dec 22;48(50):11837-9. doi: 10.1021/bi901839d.
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.
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。
