Side chain–backbone hydrogen bonding contributes to helix stability in peptides derived from an α‐helical region of carboxypeptidase A-猫眼课题宝

侧链-主链氢键有助于羧肽酶 A α 螺旋区域衍生的肽的螺旋稳定性

DOI：

发表时间：

1991

期刊：

Proteins: Structure, Function, and Bioinformatics

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

M. Bruch;M. Dhingra;L. Gierasch

最近，Presta和Rose提出1，螺旋形成的必要条件是在N-和C-末端存在残基（称为NTB和CTB），其侧链可以与螺旋的最初四个酰胺和最后四个羰基形成氢键，否则缺乏螺旋内氢键伙伴。我们已经通过圆二色性（CD）的合成肽的构象分析测试了这一假设，所述合成肽对应于蛋白质羧肽酶A的区域（171-188）;在蛋白质中，残基174至186是螺旋的，并且两侧是NTB和CTB。由于这种肽中的螺旋形成也可以通过静电相互作用来稳定，因此我们将天然肽的螺旋含量与设计用于解剖对螺旋稳定性的不同贡献的几种修饰肽的螺旋含量进行了比较。正如预期的那样，螺旋偶极相互作用似乎做出了很大贡献，但我们得出的结论是，Presta和Rose提出的氢键相互作用也稳定了螺旋的形成。为了帮助比较不同的肽，我们引入了两个浓度无关的CD参数，它们是螺旋形成的敏感探针。

Recently, Presta and Rose proposed1 that a necessary condition for helix formation is the presence of residues at the N‐and C‐termini (called NTBs and CTBs) whose side chains can form hydrogen bonds with the initial four amides and the last four carbonyls of the helix, which otherwise lack intrahelical hydrogen bonding partners. We have tested this hypothesis by conformational analysis by circular dichroism (CD) of a synthetic peptide corresponding to a region (171–188) of the protein carboxypeptidase A; in the protein, residues 174 to 186 are helical and are flanked by NTBs and CTBs. Since helix formation in this peptide may also be stabilized by electrostatic interactions, we have compared the helical content of the native peptide with that of several modified peptides designed to enable dissection of different contributions to helix stability. As expected, helix dipole interactions appear to contribute substantially, but we conclude that hydrogen bonding interactions as proposed by Presta and Rose also stabilize helix formation. To assist in comparison of different peptides, we have introduced two concentration‐independent CD parameters which are sensitive probes of helix formation.