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

Robert W. MacKintosh, Kevin N. Dalby, David G. Campbell, Patricia T. W. Cohen, Philip Cohen, Carol MacKintosh

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    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 Cys(273) of PP1 binds covalently to the methyl-dehydroalanine (Mdha) residue of the toxin, Mutation of Cys(273) 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.

    Original languageEnglish
    Pages (from-to)236-240
    Number of pages5
    JournalFEBS Letters
    Volume371
    Issue number3
    DOIs
    Publication statusPublished - 1995

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