Okadaic Acid: The Archetypal Serine / Threonine Protein Phosphatase Inhibitor

Title: Okadaic Acid: The Archetypal Serine / Threonine Protein Phosphatase Inhibitor

Volume: 9 Issue: 22

Author(s): A. B. Dounay and C. J. Forsyth

Affiliation:

Keywords: Okadaic Acid, threonine phosphatases, crystallography

Abstract: As the first recognized member of the “okadaic acid class” of phosphatase inhibitors, the marine natural product okadaic acid is perhaps the most well-known member of a diverse array of secondary metabolites that have emerged as valuable probes for studying the roles of various cellular protein serine / threonine phosphatases. This review provides a historical perspective on the role that okadaic acid has played in stimulating a broad spectrum of modern scientific research as a result of the natural products ability to bind to and inhibit important classes of protein serine / threonine phosphatases. The relationships between the structure and biological activities of okadaic acid are briefly reviewed, as well as the structural information regarding the particular cellular receptors protein phosphatases 1 (PP1) and 2A. Laboratory syntheses of okadaic acid and its analogs are thoroughly reviewed. Finally, an interpretation of the critical contacts observed between okadaic acid and PP1 by X-ray crystallography is provided, and specific molecular recognition hypotheses that are testable via the synthesis and assay of non-natural analogs of okadaic acid are suggested.

Cite this article as:

Dounay B. A. and Forsyth J. C., Okadaic Acid: The Archetypal Serine / Threonine Protein Phosphatase Inhibitor, Current Medicinal Chemistry 2002; 9 (22) . https://dx.doi.org/10.2174/0929867023368791