9MFB

Backbone alpha-Methylation in the Villin Headpiece Miniprotein: HP35 with Calpha-methyl-Lys at Position 30

これはPDB形式変換不可エントリーです。

9MFB の概要

• エントリーDOI: 10.2210/pdb9mfb/pdb
• NMR情報: BMRB: 31224
• 分子名称: Villin-1 (1 entity in total)
• 機能のキーワード: villin-1 headpiece: met12nle, lys30alphamelys, structural protein
• 由来する生物種: Gallus gallus (chicken)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4057.70

構造登録者

Harmon, T.W.,Lin, Y.,Sutton, R.T.,Osborne, S.,Horne, W.S. (登録日: 2024-12-09, 公開日: 2025-01-22, 最終更新日: 2025-03-26)

主引用文献

Harmon, T.W.,Lin, Y.,Sutton, R.T.,Osborne, S.W.J.,Seth Horne, W.
Interplay between C alpha Methylation and C alpha Stereochemistry in the Folding Energetics of a Helix-Rich Miniprotein.
Chembiochem, 26:e202401022-e202401022, 2025

PubMed Abstract: The α-helix is an abundant and functionally important element of protein secondary structure, which has motivated intensive efforts toward chemical strategies to stabilize helical folds. One such method is the incorporation of non-canonical backbone composition through an additional methyl substituent at the Cα atom. Examples of monomers include the achiral 2-aminoisobutyric acid (Aib) with geminal dimethyl substitution and chiral analogues with one methyl and one non-methyl substituent. While Aib and chiral Cα-Me residues are both established helix promoting moieties, their comparative ability in this regard has not been quantitatively investigated. Addressing this gap would help to inform the use of these building blocks in the construction of peptide and protein mimetics as well as provide fundamental insights into consequences of backbone methylation on folding. Here, we report a quantitative comparison of the impacts of Aib and chiral αMe residues on the high-resolution folded structure and folding thermodynamics of a small helical protein. These results reveal a synergistic stabilizing effect arising from the presence of Cα methylation in conjunction with a Cα stereocenter.

PubMed: 39791987
DOI: 10.1002/cbic.202401022

実験手法

SOLUTION NMR