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

被引：233

作者：

MACKINTOSH, RW

DALBY, KN

CAMPBELL, DG

COHEN, PTW

COHEN, P

MACKINTOSH, C

机构：

[1] MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee

来源：

FEBS LETTERS | 1995年 / 371卷 / 03期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

PROTEIN PHOSPHATASE; MICROCYSTIN; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION;

D O I：

10.1016/0014-5793(95)00888-G

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：236 / 240

页数：5

共 29 条

[1] INHIBITOR-2 FUNCTIONS LIKE A CHAPERONE TO FOLD 3 EXPRESSED ISOFORMS OF MAMMALIAN PROTEIN PHOSPHATASE-1 INTO A CONFORMATION WITH THE SPECIFICITY AND REGULATORY PROPERTIES OF THE NATIVE ENZYME [J].