Naturally occurring inhibitors of protein serine/threonine phosphatases

Carol MacKintosh, Julie Diplexcito

    Research output: Chapter in Book/Report/Conference proceedingChapter

    Abstract

    This chapter deals with naturally occurring inhibitors of serine and threonine phosphatases. The distinctive effects and associations of each toxin are attributable to its site of production, cell permeability, stability, abundance, and potency, for every one of these chemicals exerts its biological effects by binding tightly to active sites of protein serine/threonine phosphatases in the eukaryotic phosphoprotein phosphatase (PPP) family. This chapter begins with a description of the effects of inhibitors in cell-based experiments. It states that the use of protein phosphatase inhibitors in combination with protein kinase inhibitors and other effectors has provided clues about many signaling pathways. Following this, it discusses the binding of toxins to active sites of phosphatases. The microcystins, nodularins, okadaic acid, and tautomycin adopt similar tadpole shapes in solution, and crystal structures show that okadaic acid and microcystin-LR bind to common residues in three distinct regions of the active sites of PP1 and PP2A. Furthermore, it explains the process of chemical synthesis of protein phosphatase inhibitors, which have been a challenge to synthetic chemists, requiring innovative strategies to form multiple bonds and control many chiral centers. Finally, it deals with microcystin affinity chromatography and affinity tagging.
    Original languageEnglish
    Title of host publicationHandbook of cell signaling
    EditorsRalph A. Bradshaw, Edward A. Dennis
    Place of PublicationLondon
    PublisherAcademic Press
    Pages683-687
    Number of pages5
    Volume2
    Edition2nd
    ISBN (Print)9780123741455, 9780123741479
    DOIs
    Publication statusPublished - 2010

    Fingerprint

    Phosphoprotein Phosphatases
    Okadaic Acid
    Microcystins
    Affinity chromatography
    Protein Kinase Inhibitors
    Phosphoric Monoester Hydrolases
    Crystal structure
    Experiments

    Cite this

    MacKintosh, C., & Diplexcito, J. (2010). Naturally occurring inhibitors of protein serine/threonine phosphatases. In R. A. Bradshaw, & E. A. Dennis (Eds.), Handbook of cell signaling (2nd ed., Vol. 2, pp. 683-687). London: Academic Press. https://doi.org/10.1016/B978-0-12-374145-5.00087-5
    MacKintosh, Carol ; Diplexcito, Julie. / Naturally occurring inhibitors of protein serine/threonine phosphatases. Handbook of cell signaling. editor / Ralph A. Bradshaw ; Edward A. Dennis. Vol. 2 2nd. ed. London : Academic Press, 2010. pp. 683-687
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    MacKintosh, C & Diplexcito, J 2010, Naturally occurring inhibitors of protein serine/threonine phosphatases. in RA Bradshaw & EA Dennis (eds), Handbook of cell signaling. 2nd edn, vol. 2, Academic Press, London, pp. 683-687. https://doi.org/10.1016/B978-0-12-374145-5.00087-5

    Naturally occurring inhibitors of protein serine/threonine phosphatases. / MacKintosh, Carol; Diplexcito, Julie.

    Handbook of cell signaling. ed. / Ralph A. Bradshaw; Edward A. Dennis. Vol. 2 2nd. ed. London : Academic Press, 2010. p. 683-687.

    Research output: Chapter in Book/Report/Conference proceedingChapter

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    MacKintosh C, Diplexcito J. Naturally occurring inhibitors of protein serine/threonine phosphatases. In Bradshaw RA, Dennis EA, editors, Handbook of cell signaling. 2nd ed. Vol. 2. London: Academic Press. 2010. p. 683-687 https://doi.org/10.1016/B978-0-12-374145-5.00087-5