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

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....

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Bibliographic Details
Published in:FEBS letters 1995-09, Vol.371 (3), p.236-240
Main Authors: MacKintosh, Robert W., Dalby, Kevin N., Campbell, David G., Cohen, Patricia T.W., Cohen, Philip, MacKintosh, Carol
Format: Article
Language:English
Subjects:
Alanine - analogs & derivatives
Alanine - metabolism
Amino Acid Sequence
Bacterial Toxins - metabolism
Base Sequence
Cyanobacteria - metabolism
Cyanophyta
Cysteine - metabolism
Freshwater
Humans
Iodine Radioisotopes
Isotope Labeling
Microcystin
Microcystins
Microcystis aeruginosa
Molecular Sequence Data
Mutagenesis, Site-Directed
Peptides
Peptides, Cyclic - metabolism
Phosphoprotein Phosphatases - metabolism
Protein Binding
Protein phosphatase
Protein Phosphatase 1
Protein phosphorylation
Signal transduction
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Summary: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 IC 50 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.
ISSN:0014-5793
1873-3468
DOI:10.1016/0014-5793(95)00888-G