Glycogen and related polysaccharides inhibit the laforin dual-specificity protein phosphatase

Wei Wang, Peter J. Roach

Research output: Contribution to journalArticle

41 Scopus citations


Lafora disease, a progressive myoclonus epilepsy, is an autosomal recessive disease caused in ∼80% of cases by mutation of the EPM2A gene, which encodes a dual specificity protein phosphatase called laforin. In addition to its phosphatase domain, laforin contains an N-terminal carbohydrate-binding domain (CBD). Mouse laforin was expressed as an N-terminally polyHis tagged protein in Escherichia coli and purified close to homogeneity. The enzyme was active towards p-nitrophenylphosphate (50-80 mmol/min/mg, K m 4.5 mM) with maximal activity at pH 4.5. Laforin binds to glycogen, as previously shown, and caused potent inhibition, half maximally at ∼1 μg/ml. Less branched glucose polymers, amylopectin and amylose, were even more potent, with half maximal inhibition at 10 and 100 ng/ml, respectively. With all polysaccharides, however, inhibition was incomplete and laforin retained 20-30% of its native activity at high polysaccharide concentrations. Glucose and short oligosaccharides did not affect activity. Substitution of Trp32 in the CBD by Gly, a mutation found in a patient, caused only a 30% decrease in laforin activity but abolished binding to and inhibition by glycogen, indicating that impaired glycogen binding is sufficient to cause Lafora disease.

Original languageEnglish (US)
Pages (from-to)726-730
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Dec 17 2004


  • Dual specificity protein phosphatase
  • Glycogen
  • Glycogen binding
  • Inhibition
  • Lafora disease
  • Laforin
  • Starch

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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