Inhibition of kinesin motor proteins by adociasulfate-2

Khalilah G. Reddie, Donald R. Roberts, Timothy Dore

    Research output: Contribution to journalArticle

    Abstract

    Kinesin motor proteins are involved in cell division and intracellular transport of vesicles and organelles, and as such, they play a role in neurological disease, cancer, and developmental disorders. Inhibitors of kinesin would be valuable as probes of cell physiology and as potential therapeutics. Adociasulfate-2 (AS-2) is the only known natural product inhibitor of kinesins, but its mechanism of action is unknown. We utilized kinetic studies, dynamic light scattering, and transmission electron microscopy to investigate the inhibitory action of AS-2. Our data suggest that AS-2 is not a classical 1:1 inhibitor. Instead, a rodlike aggregate that mimics microtubules is complexed with kinesin and inhibits its ATPase activity. An intriguing implication of this hypothesis is that aggregates of a chiral natural product can have interesting and biologically relevant properties. This mode of action might represent one way in which a small molecule can disrupt a protein-protein interaction.

    Original languageEnglish (US)
    Pages (from-to)4857-4860
    Number of pages4
    JournalJournal of Medicinal Chemistry
    Volume49
    Issue number16
    DOIs
    StatePublished - Aug 10 2006

    Fingerprint

    Kinesin
    Biological Products
    Proteins
    Cell Physiological Phenomena
    Transport Vesicles
    Physiology
    Dynamic light scattering
    Light transmission
    Transmission Electron Microscopy
    Microtubules
    Organelles
    Cell Division
    Adenosine Triphosphatases
    Cells
    Transmission electron microscopy
    Molecules
    Kinetics
    adociasulfate-2
    Neoplasms
    Therapeutics

    ASJC Scopus subject areas

    • Organic Chemistry

    Cite this

    Inhibition of kinesin motor proteins by adociasulfate-2. / Reddie, Khalilah G.; Roberts, Donald R.; Dore, Timothy.

    In: Journal of Medicinal Chemistry, Vol. 49, No. 16, 10.08.2006, p. 4857-4860.

    Research output: Contribution to journalArticle

    Reddie, Khalilah G. ; Roberts, Donald R. ; Dore, Timothy. / Inhibition of kinesin motor proteins by adociasulfate-2. In: Journal of Medicinal Chemistry. 2006 ; Vol. 49, No. 16. pp. 4857-4860.
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