5wde | pdb_00005wde
Crystal structure of the KIFC3 motor domain in complex with ADP
Structural highlights
FunctionKIFC3_HUMAN Minus-end microtubule-dependent motor protein. Involved in apically targeted transport (By similarity). Required for zonula adherens maintenance.[1] Publication Abstract from PubMedKinesin 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 alpha4/alpha6 site. This selectivity can be explained by unique structural features of the KIFC1 alpha4/alpha6 binding site. These features may help improve the drug-like properties of AZ82 and other specific KIFC1 inhibitors. Structural basis of small molecule ATPase inhibition of a human mitotic kinesin motor protein.,Park HW, Ma Z, Zhu H, Jiang S, Robinson RC, Endow SA Sci Rep. 2017 Nov 9;7(1):15121. doi: 10.1038/s41598-017-14754-6. PMID:29123223[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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