Publikation:

BTB-1 : a small molecule inhibitor of the mitotic motor protein Kif18A

Lade...
Vorschaubild

Dateien

Catarinella_Angew_Chem_2009.pdf
Catarinella_Angew_Chem_2009.pdfGröße: 915.9 KBDownloads: 674

Datum

2009

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

ArXiv-ID

Internationale Patentnummer

Angaben zur Forschungsförderung

Projekt

Open Access-Veröffentlichung
Open Access Green
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

Angewandte Chemie : International Edition. 2009, 48(48), pp. 9072-9076. ISSN 1433-7851. eISSN 1521-3773. Available under: doi: 10.1002/anie.200904510

Zusammenfassung

The survival and development of each organism relies on the equal partitioning of its genome during cell division. Errors in this process can lead to severe developmental defects and cancer in humans. Key for the accurate distribution of the genome is the mitotic spindle composed of dynamic microtubules (Mts).[1] The shape and function of the mitotic spindle depends on the concerted action of various kinesins, these are molecular motor proteins which as microtubule-stimulated ATPases convert chemical energy into mechanical force. Recently, we identified the kinesin-8 member Kif18A as a central component for the correct alignment of chromosomes at the spindle equator.[2] Furthermore, in vitro analyses revealed that Kif18A distinguishes itself from all other kinesins by its dual functionality: motility and depolymerase activity.[2 4] Owing to their fast and often reversible mode of action, small molecules are ideally suited to dissect the function and mechanism of proteins. Given the complex enzymatic characteristics of Kif18A, we set up a smallmolecule screen to identify inhibitors of Kif18A. Herein we report the discovery of BTB-1 (Figure 1a), the first smallmolecule inhibitor of Kif18A. We show that BTB-1 potently inhibits the ATPase activity of Kif18A (IC50=1.69 mm) but not of other tested key mitotic kinesins. BTB-1 blocks the motility of Kif18A in a reversible manner. Notably, BTB-1 inhibits Kif18A in an adenosine triphosphate(ATP)-competitive but microtubule-uncompetitive manner and slows down the progression of cells through mitosis.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
540 Chemie

Schlagwörter

antiproliferation, enzymes, inhibitors, mitosis, molecular motors

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690CATARINELLA, Mario, Tamara GRÜNER, Tobias STRITTMATTER, Andreas MARX, Thomas U. MAYER, 2009. BTB-1 : a small molecule inhibitor of the mitotic motor protein Kif18A. In: Angewandte Chemie : International Edition. 2009, 48(48), pp. 9072-9076. ISSN 1433-7851. eISSN 1521-3773. Available under: doi: 10.1002/anie.200904510
BibTex
@article{Catarinella2009small-10061,
  year={2009},
  doi={10.1002/anie.200904510},
  title={BTB-1 : a small molecule inhibitor of the mitotic motor protein Kif18A},
  number={48},
  volume={48},
  issn={1433-7851},
  journal={Angewandte Chemie : International Edition},
  pages={9072--9076},
  author={Catarinella, Mario and Grüner, Tamara and Strittmatter, Tobias and Marx, Andreas and Mayer, Thomas U.}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/10061">
    <dc:contributor>Catarinella, Mario</dc:contributor>
    <dc:language>eng</dc:language>
    <dc:creator>Marx, Andreas</dc:creator>
    <dcterms:abstract xml:lang="eng">The survival and development of each organism relies on the equal partitioning of its genome during cell division. Errors in this process can lead to severe developmental defects and cancer in humans. Key for the accurate distribution of the genome is the mitotic spindle composed of dynamic microtubules (Mts).[1] The shape and function of the mitotic spindle depends on the concerted action of various kinesins, these are molecular motor proteins which as microtubule-stimulated ATPases convert chemical energy into mechanical force. Recently, we identified the kinesin-8 member Kif18A as a central component for the correct alignment of chromosomes at the spindle equator.[2] Furthermore, in vitro analyses revealed that Kif18A distinguishes itself from all other kinesins by its dual functionality: motility and depolymerase activity.[2 4] Owing to their fast and often reversible mode of action, small molecules are ideally suited to dissect the function and mechanism of proteins. Given the complex enzymatic characteristics of Kif18A, we set up a smallmolecule screen to identify inhibitors of Kif18A. Herein we report the discovery of BTB-1 (Figure 1a), the first smallmolecule inhibitor of Kif18A. We show that BTB-1 potently inhibits the ATPase activity of Kif18A (IC50=1.69 mm) but not of other tested key mitotic kinesins. BTB-1 blocks the motility of Kif18A in a reversible manner. Notably, BTB-1 inhibits Kif18A in an adenosine triphosphate(ATP)-competitive but microtubule-uncompetitive manner and slows down the progression of cells through mitosis.</dcterms:abstract>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/10061/1/Catarinella_Angew_Chem_2009.pdf"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:creator>Strittmatter, Tobias</dc:creator>
    <dc:creator>Mayer, Thomas U.</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:contributor>Strittmatter, Tobias</dc:contributor>
    <dc:contributor>Mayer, Thomas U.</dc:contributor>
    <dc:creator>Grüner, Tamara</dc:creator>
    <dc:contributor>Marx, Andreas</dc:contributor>
    <dcterms:bibliographicCitation>Publ. in: Angewandte Chemie : International Edition ; 48 (2009), 48. - S. 9072-9076</dcterms:bibliographicCitation>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/10061/1/Catarinella_Angew_Chem_2009.pdf"/>
    <dc:rights>terms-of-use</dc:rights>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T18:16:19Z</dc:date>
    <dcterms:title>BTB-1 : a small molecule inhibitor of the mitotic motor protein Kif18A</dcterms:title>
    <dcterms:issued>2009</dcterms:issued>
    <dc:format>application/pdf</dc:format>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:creator>Catarinella, Mario</dc:creator>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/10061"/>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dc:contributor>Grüner, Tamara</dc:contributor>
  </rdf:Description>
</rdf:RDF>

Interner Vermerk

xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter

Kontakt
URL der Originalveröffentl.

Prüfdatum der URL

Prüfungsdatum der Dissertation

Finanzierungsart

Kommentar zur Publikation

Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Diese Publikation teilen