Comparison of C−H···π and Hydrophobic Interactions in a β-Hairpin Peptide: Impact on Stability and Specificity
Comparison of C−H···π and Hydrophobic Interactions in a β-Hairpin Peptide: Impact on Stability and Specificity
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β-发夹肽中 C−H···π 和疏水相互作用的比较：对稳定性和特异性的影响
DOI：
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
M. Waters
中科院分区：
文献类型：
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作者：
C. Tatko;M. Waters
我们通过比较 Phe、Trp 或 Cha（环己基丙氨酸）与 Lys 或 Nle（正亮氨酸）的相互作用，研究了 β-发夹肽对角位置的 C-H...pi 和疏水相互作用的影响。 Lys 侧链的 NMR 研究（包括 NOESY 和化学位移扰动研究）表明，Lys 通过极化的 C epsilon 以特定的几何形状与 Phe 或 Trp 相互作用。相反，Nle 不以特定方式与对角芳族残基相互作用。热变性为 Lys 和 Nle 以根本不同的方式相互作用提供了额外的支持。发现具有对角 Trp...Lys 相互作用的肽的折叠是焓驱动的，而具有对角 Trp...Nle 相互作用的肽表现出冷变性，具有对角 Cha...Nle 相互作用的对照肽也是如此，表明 Lys 和 Nle 与 Trp 相互作用的不同驱动力。这些发现对于蛋白质折叠和从头蛋白质设计的特异性具有重要意义。
We have examined the impact of C-H...pi and hydrophobic interactions in the diagonal position of a beta-hairpin peptide through comparison of the interaction of Phe, Trp, or Cha (cyclohexylalanine) with Lys or Nle (norleucine). NMR studies, including NOESY and chemical shift perturbation studies, of the Lys side chain indicates that Lys interacts in a specific geometry with Phe or Trp through the polarized C epsilon. In contrast, Nle does not interact in a specific manner with the diagonal aromatic residue. Thermal denaturation provides additional support that Lys and Nle interact in fundamentally different manners. Folding of the peptide with a diagonal Trp...Lys interaction was found to be enthalpically driven, whereas the peptide with a diagonal Trp...Nle interaction displayed cold denaturation, as did the control peptide with a diagonal Cha...Nle interaction, indicating different driving forces for interaction of Lys and Nle with Trp. These findings have significant implications for specificity in protein folding and de novo protein design.