5VLI

Computationally designed inhibitor peptide HB1.6928.2.3 in complex with influenza hemagglutinin (A/PuertoRico/8/1934)

5VLI の概要

• エントリーDOI: 10.2210/pdb5vli/pdb
• 分子名称: Hemagglutinin, Computationally designed peptide HB1.6928.2.3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• 機能のキーワード: inhibitor, protein design, influenza, hemagglutinin, viral protein-de novo protein complex, viral protein/de novo protein
• 由来する生物種: Influenza A virus (strain A/Puerto Rico/8/1934 H1N1); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 63147.79

構造登録者

Bernard, S.M.,Wilson, I.A. (登録日: 2017-04-25, 公開日: 2017-09-27, 最終更新日: 2024-10-23)

主引用文献

Chevalier, A.,Silva, D.A.,Rocklin, G.J.,Hicks, D.R.,Vergara, R.,Murapa, P.,Bernard, S.M.,Zhang, L.,Lam, K.H.,Yao, G.,Bahl, C.D.,Miyashita, S.I.,Goreshnik, I.,Fuller, J.T.,Koday, M.T.,Jenkins, C.M.,Colvin, T.,Carter, L.,Bohn, A.,Bryan, C.M.,Fernandez-Velasco, D.A.,Stewart, L.,Dong, M.,Huang, X.,Jin, R.,Wilson, I.A.,Fuller, D.H.,Baker, D.
Massively parallel de novo protein design for targeted therapeutics.
Nature, 550:74-79, 2017

PubMed Abstract: De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

PubMed: 28953867
DOI: 10.1038/nature23912

実験手法

X-RAY DIFFRACTION (1.799 Å)