Naturally Occurring Inhibitors of Protein Serine/Threonine Phosphatases

Carol MacKintosh, Julie Diplexcito

    Research output: Chapter in Book/Report/Conference proceedingChapter


    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
    Number of pages5
    ISBN (Print)9780123741455, 9780123741479
    Publication statusPublished - 2010


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