7AVC

DoBi scaffold based on PIH1D1 N-terminal domain

これはPDB形式変換不可エントリーです。

7AVC の概要

• エントリーDOI: 10.2210/pdb7avc/pdb
• 分子名称: PIH1 domain-containing protein 1, SODIUM ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: protein scaffold, cytokine binding, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17124.44

構造登録者

Kolenko, P.,Pham, N.P.,Pavlicek, J.,Mikulecky, P.,Schneider, B. (登録日: 2020-11-05, 公開日: 2021-02-10, 最終更新日: 2024-01-31)

主引用文献

Pham, P.N.,Huliciak, M.,Biedermannova, L.,Cerny, J.,Charnavets, T.,Fuertes, G.,Herynek, S.,Kolarova, L.,Kolenko, P.,Pavlicek, J.,Zahradnik, J.,Mikulecky, P.,Schneider, B.
Protein Binder (ProBi) as a New Class of Structurally Robust Non-Antibody Protein Scaffold for Directed Evolution.
Viruses, 13:-, 2021

PubMed Abstract: Engineered small non-antibody protein scaffolds are a promising alternative to antibodies and are especially attractive for use in protein therapeutics and diagnostics. The advantages include smaller size and a more robust, single-domain structural framework with a defined binding surface amenable to mutation. This calls for a more systematic approach in designing new scaffolds suitable for use in one or more methods of directed evolution. We hereby describe a process based on an analysis of protein structures from the Protein Data Bank and their experimental examination. The candidate protein scaffolds were subjected to a thorough screening including computational evaluation of the mutability, and experimental determination of their expression yield in , solubility, and thermostability. In the next step, we examined several variants of the candidate scaffolds including their wild types and alanine mutants. We proved the applicability of this systematic procedure by selecting a monomeric single-domain human protein with a fold different from previously known scaffolds. The newly developed scaffold, called ProBi (Protein Binder), contains two independently mutable surface patches. We demonstrated its functionality by training it as a binder against human interleukin-10, a medically important cytokine. The procedure yielded scaffold-related variants with nanomolar affinity.

PubMed: 33514045
DOI: 10.3390/v13020190

実験手法

X-RAY DIFFRACTION (1.2 Å)