Helical twists and β-turns in structures at serine-proline sequences: Stabilization of cis-proline and type VI β-turns via C-H/O interactions.

IF 3.2 4区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Proteins-Structure Function and Bioinformatics Pub Date : 2024-10-01 Epub Date: 2024-05-15 DOI:10.1002/prot.26701
Harrison C Oven, Glenn P A Yap, Neal J Zondlo
{"title":"Helical twists and β-turns in structures at serine-proline sequences: Stabilization of cis-proline and type VI β-turns via C-H/O interactions.","authors":"Harrison C Oven, Glenn P A Yap, Neal J Zondlo","doi":"10.1002/prot.26701","DOIUrl":null,"url":null,"abstract":"<p><p>Structures at serine-proline sites in proteins were analyzed using a combination of peptide synthesis with structural methods and bioinformatics analysis of the PDB. Dipeptides were synthesized with the proline derivative (2S,4S)-(4-iodophenyl)hydroxyproline [hyp(4-I-Ph)]. The crystal structure of Boc-Ser-hyp(4-I-Ph)-OMe had two molecules in the unit cell. One molecule exhibited cis-proline and a type VIa2 β-turn (BcisD). The cis-proline conformation was stabilized by a C-H/O interaction between Pro C-H<sub>α</sub> and the Ser side-chain oxygen. NMR data were consistent with stabilization of cis-proline by a C-H/O interaction in solution. The other crystallographically observed molecule had trans-Pro and both residues in the PPII conformation. Two conformations were observed in the crystal structure of Ac-Ser-hyp(4-I-Ph)-OMe, with Ser adopting PPII in one and the β conformation in the other, each with Pro in the δ conformation and trans-Pro. Structures at Ser-Pro sequences were further examined via bioinformatics analysis of the PDB and via DFT calculations. Ser-Pro versus Ala-Pro sequences were compared to identify bases for Ser stabilization of local structures. C-H/O interactions between the Ser side-chain O<sub>γ</sub> and Pro C-H<sub>α</sub> were observed in 45% of structures with Ser-cis-Pro in the PDB, with nearly all Ser-cis-Pro structures adopting a type VI β-turn. 53% of Ser-trans-Pro sequences exhibited main-chain CO<sub>i</sub>•••HN<sub>i+3</sub> or CO<sub>i</sub>•••HN<sub>i+4</sub> hydrogen bonds, with Ser as the i residue and Pro as the i + 1 residue. These structures were overwhelmingly either type I β-turns or N-terminal capping motifs on α-helices or 3<sub>10</sub>-helices. These results indicate that Ser-Pro sequences are particularly potent in favoring these structures. In each, Ser is in either the PPII or β conformation, with the Ser O<sub>γ</sub> capable of engaging in a hydrogen bond with the amide N-H of the i + 2 (type I β-turn or 3<sub>10</sub>-helix; Ser χ<sub>1</sub> t) or i + 3 (α-helix; Ser χ<sub>1</sub> g<sup>+</sup>) residue. Non-proline cis amide bonds can also be stabilized by C-H/O interactions.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1190-1205"},"PeriodicalIF":3.2000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proteins-Structure Function and Bioinformatics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/prot.26701","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/15 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Structures at serine-proline sites in proteins were analyzed using a combination of peptide synthesis with structural methods and bioinformatics analysis of the PDB. Dipeptides were synthesized with the proline derivative (2S,4S)-(4-iodophenyl)hydroxyproline [hyp(4-I-Ph)]. The crystal structure of Boc-Ser-hyp(4-I-Ph)-OMe had two molecules in the unit cell. One molecule exhibited cis-proline and a type VIa2 β-turn (BcisD). The cis-proline conformation was stabilized by a C-H/O interaction between Pro C-Hα and the Ser side-chain oxygen. NMR data were consistent with stabilization of cis-proline by a C-H/O interaction in solution. The other crystallographically observed molecule had trans-Pro and both residues in the PPII conformation. Two conformations were observed in the crystal structure of Ac-Ser-hyp(4-I-Ph)-OMe, with Ser adopting PPII in one and the β conformation in the other, each with Pro in the δ conformation and trans-Pro. Structures at Ser-Pro sequences were further examined via bioinformatics analysis of the PDB and via DFT calculations. Ser-Pro versus Ala-Pro sequences were compared to identify bases for Ser stabilization of local structures. C-H/O interactions between the Ser side-chain Oγ and Pro C-Hα were observed in 45% of structures with Ser-cis-Pro in the PDB, with nearly all Ser-cis-Pro structures adopting a type VI β-turn. 53% of Ser-trans-Pro sequences exhibited main-chain COi•••HNi+3 or COi•••HNi+4 hydrogen bonds, with Ser as the i residue and Pro as the i + 1 residue. These structures were overwhelmingly either type I β-turns or N-terminal capping motifs on α-helices or 310-helices. These results indicate that Ser-Pro sequences are particularly potent in favoring these structures. In each, Ser is in either the PPII or β conformation, with the Ser Oγ capable of engaging in a hydrogen bond with the amide N-H of the i + 2 (type I β-turn or 310-helix; Ser χ1 t) or i + 3 (α-helix; Ser χ1 g+) residue. Non-proline cis amide bonds can also be stabilized by C-H/O interactions.

丝氨酸-脯氨酸序列结构中的螺旋扭曲和 β-转折:通过 C-H/O 相互作用稳定顺式脯氨酸和 VI 型 β-turns。
采用肽合成、结构方法和 PDB 生物信息学分析相结合的方法,分析了蛋白质中丝氨酸-脯氨酸位点的结构。二肽是用脯氨酸衍生物 (2S,4S)-(4-碘苯基)羟脯氨酸[hyp(4-I-Ph)]合成的。Boc-Ser-hyp(4-I-Ph)-OMe 的晶体结构在单位胞中有两个分子。其中一个分子呈现顺式脯氨酸和 VIa2 型 β-匝(BcisD)。Pro C-Hα 与 Ser 侧链氧之间的 C-H/O 相互作用稳定了顺式脯氨酸构象。核磁共振数据表明,顺式脯氨酸在溶液中通过 C-H/O 相互作用而趋于稳定。在晶体学上观察到的另一个分子中,反式脯氨酸和两个残基都处于 PPII 构象。在 Ac-Ser-hyp(4-I-Ph)-OMe 的晶体结构中观察到两种构象,一种是 Ser 采用 PPII 构象,另一种是 β 构象,每种构象都有处于 δ 构象的 Pro 和反式-Pro。通过对 PDB 进行生物信息学分析和 DFT 计算,进一步研究了 Ser-Pro 序列的结构。对 Ser-Pro 与 Ala-Pro 序列进行了比较,以确定 Ser 稳定局部结构的基础。在 PDB 中 45% 的 Ser-cis-Pro 结构中观察到了 Ser 侧链 Oγ 与 Pro C-Hα 之间的 C-H/O 相互作用,几乎所有的 Ser-cis-Pro 结构都采用了 VI 型 β 转。53% 的 Ser-trans-Pro 序列表现出主链 COi---HNi+3 或 COi---HNi+4 氢键,Ser 为 i 残基,Pro 为 i + 1 残基。这些结构绝大多数都是Ⅰ型β-转折或α-螺旋或310-螺旋上的N-末端封顶图案。这些结果表明,Ser-Pro 序列对这些结构特别有效。在每种结构中,Ser 都处于 PPII 或 β 构象中,Ser Oγ 能够与 i + 2(I 型 β 转折或 310 螺旋;Ser χ1 t)或 i + 3(α 螺旋;Ser χ1 g+)残基的酰胺 N-H 形成氢键。非脯氨酸顺式酰胺键也可以通过 C-H/O 相互作用而稳定。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Proteins-Structure Function and Bioinformatics
Proteins-Structure Function and Bioinformatics 生物-生化与分子生物学
CiteScore
5.90
自引率
3.40%
发文量
172
审稿时长
3 months
期刊介绍: PROTEINS : Structure, Function, and Bioinformatics publishes original reports of significant experimental and analytic research in all areas of protein research: structure, function, computation, genetics, and design. The journal encourages reports that present new experimental or computational approaches for interpreting and understanding data from biophysical chemistry, structural studies of proteins and macromolecular assemblies, alterations of protein structure and function engineered through techniques of molecular biology and genetics, functional analyses under physiologic conditions, as well as the interactions of proteins with receptors, nucleic acids, or other specific ligands or substrates. Research in protein and peptide biochemistry directed toward synthesizing or characterizing molecules that simulate aspects of the activity of proteins, or that act as inhibitors of protein function, is also within the scope of PROTEINS. In addition to full-length reports, short communications (usually not more than 4 printed pages) and prediction reports are welcome. Reviews are typically by invitation; authors are encouraged to submit proposed topics for consideration.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信