Tryptophan is the most prominent amino acid found in proteins, with multiple functional roles. Its side chain is made up of the hydrophobic indole moiety, with two groups that act as donors in hydrogen bonds: the Nϵ-H group, which is a potent donor in canonical hydrogen bonds, and a polarized Cδ1-H group, which is capable of forming weaker, noncanonical hydrogen bonds. Due to adjacent electron-withdrawing moieties, C-H...O hydrogen bonds are ubiquitous in macromolecules, albeit contingent on the polarization of the donor C-H group. Consequently, Cα-H groups (adjacent to the carbonyl and amino groups of flanking peptide bonds), as well as the Cϵ1-H and Cδ2-H groups of histidines (adjacent to imidazole N atoms), are known to serve as donors in hydrogen bonds, for example stabilizing parallel and antiparallel β-sheets. However, the nature and the functional role of interactions involving the Cδ1-H group of the indole ring of tryptophan are not well characterized. Here, data mining of high-resolution (r ≤ 1.5 Å) crystal structures from the Protein Data Bank was performed and ubiquitous close contacts between the Cδ1-H groups of tryptophan and a range of electronegative acceptors were identified, specifically main-chain carbonyl O atoms immediately upstream and downstream in the polypeptide chain. The stereochemical analysis shows that most of the interactions bear all of the hallmarks of proper hydrogen bonds. At the same time, their cohesive nature is confirmed by quantum-chemical calculations, which reveal interaction energies of 1.5-3.0 kcal mol-1, depending on the specific stereochemistry.

中文翻译：

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色氨酸在蛋白质中的结构作用，以及普遍存在的色氨酸 Cδ1-H...O=C（骨架）氢键。


色氨酸是蛋白质中最重要的氨基酸，具有多种功能。它的侧链由疏水性吲哚部分组成，具有两个充当氢键供体的基团：Nϵ-H基团，它是典型氢键中的有效供体，以及极化的Cδ1-H基团，它能够形成较弱的非规范氢键。由于相邻的吸电子部分，CH...O 氢键在大分子中普遍存在，尽管取决于供体 CH 基团的极化。因此，Cα-H 基团（与侧翼肽键的羰基和氨基相邻）以及组氨酸的 Cϵ1-H 和 Cδ2-H 基团（与咪唑 N 原子相邻）已知可作为氢的供体键，例如稳定平行和反平行 β-折叠。然而，涉及色氨酸吲哚环 Cδ1-H 基团的相互作用的性质和功能作用尚未得到很好的表征。在这里，对蛋白质数据库中的高分辨率 (r ≤ 1.5 Å) 晶体结构进行了数据挖掘，并鉴定了色氨酸的 Cδ1-H 基团和一系列负电受体之间普遍存在的紧密接触，特别是主链羰基 O紧邻多肽链上游和下游的原子。立体化学分析表明，大多数相互作用都具有适当氢键的所有特征。同时，它们的内聚性质得到了量子化学计算的证实，计算结果表明，根据具体的立体化学，相互作用能为 1.5-3.0 kcal mol-1。