THE CYANOBACTERIAL TOXIN MICROCYSTIN BINDS COVALENTLY TO CYSTEINE-273ON PROTEIN PHOSPHATASE-1

The interaction between protein phosphatase 1 (PP1) and microcystin (M C) was stable in 1% SDS or 70% formic acid indicative of a covalent in teraction, Here we isolate the MC-binding peptide and demonstrate that Cys(273) of PP1 binds covalently to the methyl-dehydroalanine (Mdha) residue of the toxin, Mutation of Cys(273) to Ala, Ser or Leu abolishe d covalent binding to MC, as did reduction of the Mdha residue of the toxin with ethanethiol, The abolition of covalent binding increased th e IC50 for toxin inhibition of PP1 by 5- to 20-fold, The covalent bind ing of MC to protein serine/threonine phosphatases explains the failur e to detect this toxin post-mortem in suspected cases of MC poisoning.