The cyanobacterial toxin microcystin binds covalently to cysteine‐273 on protein phosphatase 1

Abstract

The interaction between protein phosphatase 1 (PP1) and microcystin (MC) was stable in 1% SDS or 70% formic acid indicative of a covalent interaction. Here we isolate the MC‐binding peptide and demonstrate that Cys²⁷³ of PP1 binds covalently to the methyl‐dehydroalanine (Mdha) residue of the toxin. Mutation of Cys²⁷³ to Ala, Ser or leu abolished covalent binding to MC, as did reduction of the Mdha residue of the toxin with ethanethiol. The abolition of covalent binding increased the IC₅₀ for toxin inhibition of PP1 by 5‐ to 20‐fold. The covalent binding of MC to protein serine/threonine phosphatases explains the failure to detect this toxin post‐mortem in suspected cases of MC poisoning.