3WPN

Kinesin spindle protein Eg5 in complex with ATP-competitive inhibitor PVZB1194

3WPN の概要

• エントリーDOI: 10.2210/pdb3wpn/pdb
• 関連するPDBエントリー: 1II6 1Q0B 3ZCW
• 分子名称: Kinesin-like protein KIF11, 3'-fluoro-4'-(trifluoromethyl)biphenyl-4-sulfonamide (3 entities in total)
• 機能のキーワード: cell cycle, motor domain, atp binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P52732
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43194.91

構造登録者

Yokoyama, H.,Katoh, S.,Fujii, S. (登録日: 2014-01-14, 公開日: 2015-01-21, 最終更新日: 2023-11-08)

主引用文献

Yokoyama, H.,Sawada, J.,Katoh, S.,Matsuno, K.,Ogo, N.,Ishikawa, Y.,Hashimoto, H.,Fujii, S.,Asai, A.
Structural basis of new allosteric inhibition in Kinesin spindle protein eg5
Acs Chem.Biol., 10:1128-1136, 2015

PubMed Abstract: Kinesin spindle protein Eg5 is a target for anticancer therapies, and small molecule inhibitors of its ATPase activity have been developed. We herein report for the first time the crystal structure of and biochemical studies on the Eg5 motor domain in complex with a new type of allosteric inhibitor. The biphenyl-type inhibitor PVZB1194 binds to the α4/α6 allosteric pocket 15 Å from the ATP-binding pocket, which differs from conventional allosteric inhibitors that bind to the allosteric L5/α2/α3 pocket of Eg5. Binding of the inhibitor is involved in the neck-linker conformation and also causes conformational changes around the ATP-binding pocket through Tyr104 to affect the interaction of ATP with the pocket. This structure provides useful information for the development of novel types of allosteric drugs as well as a novel insight into the molecular mechanism responsible for regulating the motor activity of kinesins.

PubMed: 25622007
DOI: 10.1021/cb500939x

実験手法

X-RAY DIFFRACTION (2.8 Å)