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PDBsum entry 3zcw
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PDB id:
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Cell cycle
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Title:
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Eg5 - new allosteric binding site
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Structure:
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Kinesin-like protein kif11. Chain: a. Fragment: motor domain, residues 16-363. Synonym: kinesin-like protein 1, kinesin-like spindle protein hksp, kinesin-related motor protein eg5, thyroid receptor-interacting protein 5, tr-interacting protein 5, trip-5. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_variant: codon plus.
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Resolution:
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1.69Å
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R-factor:
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0.196
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R-free:
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0.233
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Authors:
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V.Ulaganathan,S.K.Talapatra,F.Kozielski,A.D.Pannifer
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Key ref:
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V.Ulaganathan
et al.
(2013).
Structural insights into a unique inhibitor binding pocket in kinesin spindle protein.
J Am Chem Soc,
135,
2263-2272.
PubMed id:
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Date:
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23-Nov-12
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Release date:
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23-Jan-13
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PROCHECK
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Headers
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References
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P52732
(KIF11_HUMAN) -
Kinesin-like protein KIF11 from Homo sapiens
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Seq:
Struc:
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1056 a.a.
321 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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J Am Chem Soc
135:2263-2272
(2013)
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PubMed id:
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Structural insights into a unique inhibitor binding pocket in kinesin spindle protein.
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V.Ulaganathan,
S.K.Talapatra,
O.Rath,
A.Pannifer,
D.D.Hackney,
F.Kozielski.
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ABSTRACT
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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.
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