Corozalic acid: a key okadaic acid biosynthetic precursor with phosphatase inhibition activity

Chemistry. 2010 Oct 11;16(38):11576-9. doi: 10.1002/chem.201001327. Epub 2010 Aug 27.

Abstract

Toxin precursors: Corozalic acid, a new Ser/Thr protein phosphatase 1 and 2A inhibitor that turned out to be a key metabolic intermediate, was isolated from cultures of the marine dinoflagellate Prorocentrum belizeanum. Detailed spectroscopic analysis and extensive computational calculations revealed its structure and conformational behavior. In addition, a comprehensive picture of the interactions of corozalic acid with PP1 and PP2A is proposed (see figure) on the basis of ab initio, docking and molecular dynamics calculations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Dinoflagellida / chemistry
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Molecular Docking Simulation
  • Okadaic Acid / analogs & derivatives*
  • Okadaic Acid / chemistry*
  • Protein Phosphatase 1 / antagonists & inhibitors*
  • Protein Phosphatase 1 / metabolism
  • Protein Phosphatase 2 / antagonists & inhibitors*
  • Protein Phosphatase 2 / metabolism
  • Thermodynamics

Substances

  • Enzyme Inhibitors
  • corozalic acid
  • Okadaic Acid
  • Protein Phosphatase 1
  • Protein Phosphatase 2