PDBsum entry 3zcw

Cell cycle

PDB id: 3zcw

Contents

Protein chain

321 a.a.

Ligands

ADP

4A2 ×2

EPE

PEG

Metals

_MG

Waters ×450

References listed in PDB file

Key reference

• Title: Structural insights into a unique inhibitor binding pocket in kinesin spindle protein.
• Authors: V.Ulaganathan, S.K.Talapatra, O.Rath, A.Pannifer, D.D.Hackney, F.Kozielski.
• Ref.: J Am Chem Soc, 2013, 135, 2263-2272.
• PubMed id: 23305346

Abstract

Human kinesin Eg5 is a target for drug development in cancer chemotherapy with compounds in phase II clinical trials. These agents bind to a well-characterized allosteric pocket involving the loop L5 region, a structural element in kinesin-5 family members thought to provide inhibitor specificity. Using X-ray crystallography, kinetic, and biophysical methods, we have identified and characterized a distinct allosteric pocket in Eg5 able to bind inhibitors with nanomolar K(d). This pocket is formed by key structural elements thought to be pivotal for force generation in kinesins and may represent a novel site for therapeutic intervention in this increasingly well-validated drug target.