5KNG

CRYSTAL STRUCTURE OF ANTI-IL-13 DARPIN 6G9

5KNG の概要

• エントリーDOI: 10.2210/pdb5kng/pdb
• 関連するPDBエントリー: 5KNH
• 分子名称: DARPIN 6G9, PHOSPHATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: alternative scaffold, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 73351.57

構造登録者

Teplyakov, A.,Malia, T.,Obmolova, G.,Gilliland, G. (登録日: 2016-06-28, 公開日: 2016-12-14, 最終更新日: 2023-09-27)

主引用文献

Teplyakov, A.,Malia, T.J.,Obmolova, G.,Jacobs, S.A.,O'Neil, K.T.,Gilliland, G.L.
Conformational flexibility of an anti-IL-13 DARPin.
Protein Eng. Des. Sel., 30:31-37, 2017

PubMed Abstract: Designed ankyrin repeat proteins (DARPin) are artificial non-immunoglobulin binding proteins with potential applications as therapeutic molecules. DARPin 6G9 binds interleukin-13 with high affinity and blocks the signaling pathway and as such is promising for the treatment of asthma and other atopic diseases. The crystal structures of DARPin 6G9 in the unbound form and in complex with IL-13 were determined at high resolution. The DARPin competes for the same epitope as the IL-13 receptor chain 13Rα1 but does not interfere with the binding of the other receptor chain, IL-4Rα. Analysis of multiple copies of the DARPin molecule in the crystal indicates the conformational instability in the N-terminal cap that was predicted from molecular dynamics simulations. Comparison of the DARPin structures in the free state and in complex with IL-13 reveals a concerted movement of the ankyrin repeats upon binding resulted in the opening of the binding site. The induced-fit mode of binding employed by DARPin 6G9 is very unusual for DARPins since they were designed as particularly stable and rigid molecules. This finding shows that DARPins can operate by various binding mechanisms and suggests that some flexibility in the scaffold may be an advantage.

PubMed: 27881684
DOI: 10.1093/protein/gzw059

実験手法

X-RAY DIFFRACTION (1.35 Å)