Characterization of a mutant alpha-galactosidase gene product for the late-onset cardiac form of Fabry disease

Biochem Biophys Res Commun. 1993 Dec 30;197(3):1585-9. doi: 10.1006/bbrc.1993.2659.


The expression product of a mutant alpha-galactosidase gene, Q279E (279Gln-->Glu), found in an atypical variant (cardiac form) of Fabry disease, was purified and characterized. It had kinetic properties similar to those of normal alpha-galactosidase, but was markedly thermolabile at neutral pH. Galactose and melibiose at high concentrations stabilized the mutant enzyme in vitro. Its catalytic activity was 15% of that for the normal enzyme, when it was expressed in COS-1 cells at 37 degrees C. The activity increased at 30 degrees C or in the presence of galactose at 37 degrees C. An increase was also observed in lymphoblasts from a patient with this mutation in the presence of galactose or melibiose. We conclude that this mutant protein is posttranslationally inactivated under the neutral conditions in the cells. The possibility of a new therapeutic approach is suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Enzyme Stability
  • Fabry Disease / enzymology*
  • Fabry Disease / genetics*
  • Galactose / pharmacology
  • Gene Expression
  • Genetic Variation
  • Glutamates
  • Glutamic Acid
  • Glutamine
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Lymphocytes / drug effects
  • Lymphocytes / enzymology
  • Melibiose / pharmacology
  • Point Mutation*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Thermodynamics
  • Transfection
  • alpha-Galactosidase / genetics*
  • alpha-Galactosidase / metabolism


  • Glutamates
  • Recombinant Proteins
  • Glutamine
  • Glutamic Acid
  • Melibiose
  • alpha-Galactosidase
  • Galactose