9D9C

Incorporation of dehydro-aza-proline residues in avian pancreatic polypeptide: Aza-Pro substitution at positions 4 and 6

これはPDB形式変換不可エントリーです。

9D9C の概要

• エントリーDOI: 10.2210/pdb9d9c/pdb
• NMR情報: BMRB: 31197
• 分子名称: Pancreatic polypeptide (1 entity in total)
• 機能のキーワード: pancreatic hormone, modified backbone, signaling protein
• 由来する生物種: Meleagris gallopavo (turkey)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 8407.14

構造登録者

Wright, M.M.,Rajewski, B.H.,Gerrein, T.A.,Smith, L.J.,Horne, W.S.,Del Valle, J.R. (登録日: 2024-08-21, 公開日: 2025-04-02)

主引用文献

Wright, M.M.,Rajewski, B.H.,Gerrein, T.A.,Xu, Z.,Smith, L.J.,Seth Horne, W.,Del Valle, J.R.
Stabilization of a miniprotein fold by an unpuckered proline surrogate.
Commun Chem, 8:76-76, 2025

PubMed Abstract: The unique role of proline in modulating protein folding and recognition makes it an attractive target for substitution to generate new proteomimetics. The design, synthesis, and conformational analysis of non-canonical surrogates can also aid in parsing the role of prolyl stereoelectronic effects on structure. We recently described the synthesis and conformational analysis of dehydro-δ-azaproline (ΔaPro), a novel unsaturated analogue of proline featuring a planar dehydropyrazine ring. When incorporated into host sequences, this backbone N-aminated proline surrogate forms an acylhydrazone bond with an unusually high trans rotamer bias and low isomerization barrier. Here, we used CD, NMR spectroscopy, and MD simulations to evaluate the impact of ΔaPro substitution within the polyproline II (PPII) and loop regions of the avian pancreatic polypeptide (aPP). The ΔaPro residue strongly favors PPII conformation and stabilizes the aPP tertiary fold when incorporated at select positions within the miniprotein. A variant featuring three ΔaPro substitutions was found to significantly enhance the thermal stability of wild-type aPP despite compromising protein dimerization. Our results suggest that the stability of proline-rich folds relies more on backbone torsional preferences than ring puckering and informs strategies for the incorporation of ΔaPro into thermally stable and functional proteomimetics.

PubMed: 40075167
DOI: 10.1038/s42004-025-01474-6

実験手法

SOLUTION NMR