6NAF

De novo designed homo-trimeric amantadine-binding protein

6NAF の概要

• エントリーDOI: 10.2210/pdb6naf/pdb
• 関連するPDBエントリー: 6N9H
• 分子名称: amantadine-binding protein, (3S,5S,7S)-tricyclo[3.3.1.1~3,7~]decan-1-amine, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: helical bundle, trimer, amantadine-binding protein, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9313.75

構造登録者

Selvaraj, B.,Park, J.,Cuneo, M.J.,Myles, D.A.A.,Baker, D. (登録日: 2018-12-05, 公開日: 2019-12-18, 最終更新日: 2023-10-25)

主引用文献

Park, J.,Selvaraj, B.,McShan, A.C.,Boyken, S.E.,Wei, K.Y.,Oberdorfer, G.,DeGrado, W.,Sgourakis, N.G.,Cuneo, M.J.,Myles, D.A.,Baker, D.
De novo design of a homo-trimeric amantadine-binding protein.
Elife, 8:-, 2019

PubMed Abstract: The computational design of a symmetric protein homo-oligomer that binds a symmetry-matched small molecule larger than a metal ion has not yet been achieved. We used de novo protein design to create a homo-trimeric protein that binds the C symmetric small molecule drug amantadine with each protein monomer making identical interactions with each face of the small molecule. Solution NMR data show that the protein has regular three-fold symmetry and undergoes localized structural changes upon ligand binding. A high-resolution X-ray structure reveals a close overall match to the design model with the exception of water molecules in the amantadine binding site not included in the Rosetta design calculations, and a neutron structure provides experimental validation of the computationally designed hydrogen-bond networks. Exploration of approaches to generate a small molecule inducible homo-trimerization system based on the design highlight challenges that must be overcome to computationally design such systems.

PubMed: 31854299
DOI: 10.7554/eLife.47839

実験手法

NEUTRON DIFFRACTION (2.5 Å)
X-RAY DIFFRACTION (1.923 Å)