3WPN

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

Summary for 3WPN

• Entry DOI: 10.2210/pdb3wpn/pdb
• Related: 1II6 1Q0B 3ZCW
• Descriptor: Kinesin-like protein KIF11, 3'-fluoro-4'-(trifluoromethyl)biphenyl-4-sulfonamide (3 entities in total)
• Functional Keywords: cell cycle, motor domain, atp binding
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P52732
• Total number of polymer chains: 1
• Total formula weight: 43194.91

Authors

Yokoyama, H.,Katoh, S.,Fujii, S. (deposition date: 2014-01-14, release date: 2015-01-21, Last modification date: 2023-11-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)