5US3

Heterogeneous-backbone Foldamer Mimic of the Sp1-3 Zinc Finger

5US3 の概要

• エントリーDOI: 10.2210/pdb5us3/pdb
• NMR情報: BMRB: 30244
• 分子名称: Heterogeneous-Backbone Variant of the Sp1-3 Zinc Finger: N-Me-Ala3, N-Me-Arg10, beta-3-Asp15, beta-3-Lys19, beta3-Lys22, beta-3-Gln25, ZINC ION (2 entities in total)
• 機能のキーワード: zinc finger, heterogeneous backbone, foldamer, de novo protein
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3549.58

構造登録者

George, K.L.,Horne, W.S. (登録日: 2017-02-13, 公開日: 2017-05-31, 最終更新日: 2024-07-10)

主引用文献

George, K.L.,Horne, W.S.
Heterogeneous-Backbone Foldamer Mimics of Zinc Finger Tertiary Structure.
J. Am. Chem. Soc., 139:7931-7938, 2017

PubMed Abstract: A variety of oligomeric backbones with compositions deviating from biomacromolecules can fold in defined ways. Termed "foldamers," these agents have diverse potential applications. A number of protein-inspired secondary structures (e.g., helices, sheets) have been produced from unnatural backbones, yet examples of tertiary folds combining several secondary structural elements in a single entity are rare. One promising strategy to address this challenge is the systematic backbone alteration of natural protein sequences, through which a subset of the native side chains is displayed on an unnatural building block to generate a heterogeneous backbone. A drawback to this approach is that substitution at more than one or two sites often comes at a significant energetic cost to fold stability. Here we report heterogeneous-backbone foldamers that mimic the zinc finger domain, a ubiquitous and biologically important metal-binding tertiary motif, and do so with a folded stability that is superior to the natural protein on which their design is based. A combination of UV-vis spectroscopy, isothermal titration calorimetry, and multidimensional NMR reveals that suitably designed oligomers with >20% modified backbones can form native-like tertiary folds with metal-binding environments identical to the prototype sequence (the third finger of specificity factor 1) and enhanced thermodynamic stability. These results expand the scope of heterogeneous-backbone foldamer design to a new tertiary structure class and show that judiciously applied backbone modification can be accompanied by improvement to fold stability.

PubMed: 28509549
DOI: 10.1021/jacs.7b03114

実験手法

SOLUTION NMR