Alanine is an intrinsic α-helix stabilizing amino acid
Alanine is an intrinsic α-helix stabilizing amino acid
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DOI：
10.1021/ja990056x
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发表时间：
1999-06-16
影响因子：
15
通讯作者：
Kallenbach, NR
中科院分区：
文献类型：
--
作者：
Spek, EJ;Olson, CA;Kallenbach, NR
大的蛋白质通过中间结构的形成折叠。1这些中间体是否具有二级结构，如R-螺旋或β-折叠？一个相关的问题是特定的氨基酸侧链是否具有形成初始或最终二级结构的内在趋势。关于丙氨酸的螺旋倾向存在持续的争论。对有核肽和辅助多肽的研究得出结论，丙氨酸是螺旋无关的;对蛋白质和肽的其他研究得出结论，丙氨酸是螺旋稳定的。4-6 Scheraga等人合成了辅多肽，其中Ala序列的侧翼是带电侧链的延伸嵌段，并得出结论，丙氨酸的短片段（低于N100个残基）不会形成R-螺旋。2将天然氨基酸作为客体引入烷基化谷氨酰胺残基的宿主基质中3似乎证实了Ala是螺旋无关的。尽管如此，发现许多富含丙氨酸的短肽模型形成R-螺旋结构，4-6并且丙氨酸稳定蛋白质中的螺旋。[7]因此，我们对R-螺旋结构及其在折叠中的作用的理解存在根本矛盾。Ala要么稳定R-螺旋，要么不稳定。
Large proteins fold via the formation of intermediate structures. 1 Do these intermediates possess secondary structure such as an R-helix or β-sheets? A related question is whether specific amino acid side chains have an intrinsic tendency to form incipient or final secondary structure. There is an ongoing debate concerning the helix propensity of alanine. Studies on nucleated peptides and co-polypeptides conclude that alanine is helix-indifferent; other studies on proteins and peptides conclude that alanine is helixstabilizing. 4-6Scheraga et al. synthesized co-polypeptides in which Ala sequences were flanked by extended blocks of charged side chains and concluded that short stretches of alanine (below N≈ 100 residues) do not form an R-helix. 2 Introducing natural amino acids as guests into a host matrix of alkylated glutamine residues3 seemingly confirmed that Ala is helix-indifferent. Still, many alanine-rich short peptide models are found to form R-helical structure, 4-6 and alanine stabilizes helices in proteins. 7 There is then a fundamental contradiction in our understanding of R-helical structure and its role in folding. Either Ala stabilizes R-helices, or it does not.