TY - JOUR
T1 - The cyanobacterial toxin microcystin binds covalently to cysteine-273 on protein phosphatase 1
AU - MacKintosh, Robert W.
AU - Dalby, Kevin N.
AU - Campbell, David G.
AU - Cohen, Patricia T. W.
AU - Cohen, Philip
AU - MacKintosh, Carol
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
U2 - 10.1016/0014-5793(95)00888-G
DO - 10.1016/0014-5793(95)00888-G
M3 - Article
SN - 0014-5793
VL - 371
SP - 236
EP - 240
JO - FEBS Letters
JF - FEBS Letters
IS - 3
ER -