Amide Nitrogen Pyramidalization via N-H/N Interactions that Stabilize the δ/α Conformations in Turns, Loops, and 310- and α-Helices.

IF 3.8 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Noah J Daniecki, Glenn P A Yap, Neal J Zondlo
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引用次数: 0

Abstract

N-H/N interactions, between an amide N-H on one residue (i + 1) and the amide N lone pair on the prior (i) residue, have been observed in key structures in proteins, including turns, loops, and α-helices. However, there remains an incomplete understanding about the inherent nature of N-H/N interactions and how they can impact protein structure and dynamics. The crystal structure of a molecule (Boc-hyp(4-I-Ph)-NHCy) with an N-Hi+1/Ni interaction was obtained. This structure had a close Hi+1···Ni distance of 2.30 Å, well below the 2.75 Å sum of the van der Waals radii of H and N. This structure exhibited substantial (12°; 0.17 Å) pyramidalization (partial sp3 character) of the proline Ni nitrogen. This pyramidalization reduces the planarity and electron delocalization inherent to an amide bond, as a result of the nitrogen Ni lone pair engaging directly with the hydrogen on the subsequent amide. DFT calculations on Ac-Pro-NHMe indicate that nitrogen pyramidalization and partial loss of amide planarity are inherent features of an N-H/N interaction. In addition, calculations demonstrate that the δ conformation, which has an N-H/N interaction, exhibits a substantially lower barrier to proline cis-trans isomerism than the PPII conformation, which lacks an N-H/N interaction, and that a closer N-H/N interaction and greater N pyramidalization are observed in the transition state than in the ground states. Analysis of small-molecule crystal structures indicates that close H···N distances and substantial Ni pyramidalization are inherent to N-H/N interactions. N-H/N interactions are ubiquitous in the PDB at all 20 canonical amino acids when they are in the δ/αR or δ'/αL conformations, consistent with N-H/N interactions being central local structural elements in proteins, as well as in early folding transitions in proteins (single residue δ/αR → type I β-turn → 310-helix → α-helix).

酰胺氮金字塔化通过N- h /N相互作用稳定在匝、环、310-和α-螺旋中的δ/α构象。
在一个残基(i + 1)上的酰胺N- h与前一个残基(i)上的酰胺N孤对之间的N- h /N相互作用,已经在蛋白质的关键结构中观察到,包括旋转、环和α-螺旋。然而,人们对N- h /N相互作用的内在性质以及它们如何影响蛋白质结构和动力学的理解仍然不完整。得到了具有N-Hi+1/Ni相互作用的Boc-hyp(4-I-Ph)-NHCy分子的晶体结构。该结构的Hi+1···Ni距离为2.30 Å,远低于H和n的范德华半径之和2.75 Å。该结构显示了大量(12°;0.17 Å)脯氨酸Ni氮的锥体化(部分sp3特征)。由于氮镍孤对直接与随后的酰胺上的氢结合,这种金字塔化降低了酰胺键固有的平面性和电子离域。Ac-Pro-NHMe的DFT计算表明,氮锥体化和酰胺平面度的部分损失是N- h /N相互作用的固有特征。此外,计算表明,具有N- h /N相互作用的δ构象比缺乏N- h /N相互作用的PPII构象具有更低的脯氨酸顺反异构障碍,并且在过渡态比基态观察到更紧密的N- h /N相互作用和更大的N金字塔化。对小分子晶体结构的分析表明,紧密的H···N距离和大量的Ni锥体化是N-H/N相互作用所固有的。当20种典型氨基酸处于δ/αR或δ'/αL构象时,它们的PDB中普遍存在N- h /N相互作用,这与N- h /N相互作用是蛋白质的中心局部结构元件以及蛋白质的早期折叠转变(单残基δ/αR→I型β-turn→310-螺旋→α-螺旋)一致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Chemical Biology
ACS Chemical Biology 生物-生化与分子生物学
CiteScore
7.50
自引率
5.00%
发文量
353
审稿时长
3.3 months
期刊介绍: ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology. The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies. We welcome mechanistic studies on proteins, nucleic acids, sugars, lipids, and nonbiological polymers. The journal serves a large scientific community, exploring cellular function from both chemical and biological perspectives. It is understood that submitted work is based upon original results and has not been published previously.
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