5OEH

Molecular tweezers modulate 14-3-3 protein-protein interactions.

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5OEH の概要

• エントリーDOI: 10.2210/pdb5oeh/pdb
• 分子名称: 14-3-3 protein sigma, (1R,5S,9S,16R,20R,24S,28S,35R)-3,22-Bis(dihydroxyphosphoryloxy)tridecacyclo[22.14.1.15,20.19,16.128,35.02,23.04,21.06,19.08,17.010,15.025,38.027,36.029,34]dotetraconta-2(23),3,6,8(17),10,12,14,18,21,25,27(36),29,31,33,37-pentadecaene, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: 14-3-3 protein, inhibition, supramolecular ligands, signaling protein
• 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: 27397.11

構造登録者

Bier, D.,Ottmann, C. (登録日: 2017-07-07, 公開日: 2017-07-26, 最終更新日: 2024-01-17)

主引用文献

Bier, D.,Rose, R.,Bravo-Rodriguez, K.,Bartel, M.,Ramirez-Anguita, J.M.,Dutt, S.,Wilch, C.,Klarner, F.G.,Sanchez-Garcia, E.,Schrader, T.,Ottmann, C.
Molecular tweezers modulate 14-3-3 protein-protein interactions.
Nat Chem, 5:234-239, 2013

PubMed Abstract: Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule). We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins. The tweezers inhibit binding between the 14-3-3 protein and two partner proteins--a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)--in a concentration-dependent manner. Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins. A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein-protein interactions.

PubMed: 23422566
DOI: 10.1038/nchem.1570

実験手法

X-RAY DIFFRACTION (2.35 Å)