Evidence map›Paper›PMID 29123223›Full record

ArticleScientific reports2017

Structural basis of small molecule ATPase inhibition of a human mitotic kinesin motor protein.

Hee-Won Park, Zhujun Ma, Haizhong Zhu, Shimin Jiang, Robert C Robinson, Sharyn A Endow

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 35 citations in OpenAlex.

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  14. Mitotic Motor KIFC1 Is an Organizer of Microtubules in the Axon.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019
    Article
  15. Cancer drug therapy and stochastic modeling of "nano-motors".International journal of nanomedicine · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 4 countries.

Hee-Won ParkStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
Zhujun MaNeuroscience & Behavioural Disorders Programme, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore.
Haizhong ZhuStructural Genomics Consortium, University of Toronto, Toronto, ON M5G 1L7, Canada.
Shimin JiangInstitute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore, 138673, Singapore.
Robert C RobinsonInstitute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore, 138673, Singapore.
Sharyn A EndowNeuroscience & Behavioural Disorders Programme, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore. sharyn.endow@duke.edu.
National University of Singapore · SGStructural Genomics Consortium · CAInstitute of Molecular and Cell Biology · SGNanyang Technological University · SG

Funding

Overall (pp. 40-62)P41GM103485 · NIGMS · CORNELL UNIVERSITY · PI CERIONE, RICHARD A. · 2012 to 2018
$15.5M
NIGMS NIH HHS P41 GM103485Wellcome Trust
6 · The paper itself

Abstract

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.

Indexed as

AlanineBinding SitesCrystallography, X-RayDrosophila ProteinsEnzyme InhibitorsHumansKinesinsModels, MolecularProtein BindingProtein ConformationPyridines5-methyl-N-(1-oxo-1-(pyrrolidin-3-ylamino)-3-(6-(3-(trifluoromethoxy)phenyl)pyridin-3-yl)propan-2-yl)-4-propylthiophene-2-carboxamideAlanineDrosophila ProteinsEnzyme InhibitorsKIF1C protein, humanKifc3 protein, humanKinesinsncd protein, DrosophilaPyridines

Identifiers

PMID29123223
PMCPMC5680195
OpenAlexW2766016615

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.