Evidence map›Paper›PMID 23658017›Full record

ArticleThe Journal of biological chemistry2013

"Snapshots" of ispinesib-induced conformational changes in the mitotic kinesin Eg5.

Hung Yi Kristal Kaan, Jennifer Major, Katarzyna Tkocz, Frank Kozielski, Steven S Rosenfeld

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 27% 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

14 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Design, synthesis, molecular docking, andSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024
    Article
  3. Optical Control of Mitosis with a Photoswitchable Eg5 Inhibitor.Angewandte Chemie (International ed. in English) · 2022
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Kinesin, 30 years later: Recent insights from structural studies.Protein science : a publication of the Protein Society · 2015
    Review
  14. 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

5 authors at 2 institutions in 2 countries.

Hung Yi Kristal KaanBeatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, Scotland, United Kingdom.
Jennifer Major
Katarzyna Tkocz
Frank Kozielski
Steven S Rosenfeld
Cancer Research UK Scotland Institute · GBCleveland Clinic Lerner College of Medicine · US

Funding

Mechanisms of Processivity in Molecular MotorsR01GM102875 · NIGMS · CLEVELAND CLINIC LERNER COM-CWRU · PI YI, QING · 2012 to 2015
$1.2M
NIGMS NIH HHS GM102875NIGMS NIH HHS R01 GM102875
6 · The paper itself

Abstract

Kinesins comprise a superfamily of molecular motors that drive a wide variety of cellular physiologies, from cytoplasmic transport to formation of the bipolar spindle in mitosis. These differing roles are reflected in corresponding polymorphisms in key kinesin structural elements. One of these is a unique loop and stem motif found in all kinesins and referred to as loop 5 (L5). This loop is longest in the mitotic kinesin Eg5 and is the target for a number of small molecule inhibitors, including ispinesib, which is being used in clinical trials in patients with cancer. In this study, we have used x-ray crystallography to identify a new structure of an Eg5-ispinesib complex and have combined this with transient state kinetics to identify a plausible sequence of conformational changes that occur in response to ispinesib binding. Our results demonstrate that ispinesib-induced structural changes in L5 from Eg5 lead to subsequent changes in the conformation of the switch II loop and helix and in the neck linker. We conclude that L5 in Eg5 simultaneously regulates the structure of both the ATP binding site and the motor's mechanical elements that generate force.

Indexed as

Protein Structure, TertiaryAlgorithmsBenzamidesBinding SitesBiocatalysisCrystallography, X-RayHumansKinesinsKineticsMitosisModels, MolecularMolecular StructureProtein BindingProtein ConformationProtein Structure, SecondaryQuinazolinesBenzamidesispinesibKIF11 protein, humanKinesinsQuinazolinesCrystal StructureFluorescence Resonance Energy Transfer (FRET)KinesinKineticsMitosis

Identifiers

PMID23658017
PMCPMC3689998
OpenAlexW2001219990

What OpenQuestion holds

Textmetadata
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.