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PDBsum entry 5w3d
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Motor protein
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PDB id
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5w3d
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References listed in PDB file
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Key reference
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Title
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Structural basis of small molecule atpase inhibition of a human mitotic kinesin motor protein.
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Authors
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H.W.Park,
Z.Ma,
H.Zhu,
S.Jiang,
R.C.Robinson,
S.A.Endow.
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Ref.
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Sci Rep, 2017,
7,
15121.
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PubMed id
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Abstract
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Kinesin microtubule motor proteins play essential roles in division, including
attaching chromosomes to spindles and crosslinking microtubules for spindle
assembly. Human kinesin-14 KIFC1 is unique in that cancer cells with amplified
centrosomes are dependent on the motor for viable division because of its
ability to cluster centrosomes and form bipolar spindles, but it is not required
for division in almost all normal cells. Screens for small molecule inhibitors
of KIFC1 have yielded several candidates for further development, but obtaining
structural data to determine their sites of binding has been difficult. Here we
compare a previously unreported KIFC1 crystal structure with new structures of
two closely related kinesin-14 proteins, Ncd and KIFC3, to determine the
potential binding site of a known KIFC1 ATPase inhibitor, AZ82. We analyze the
previously identified kinesin inhibitor binding sites and identify features of
AZ82 that favor binding to one of the sites, the α4/α6 site. This selectivity
can be explained by unique structural features of the KIFC1 α4/α6 binding
site. These features may help improve the drug-like properties of AZ82 and other
specific KIFC1 inhibitors.
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