title: Characterization of a mutant alpha-galactosidase gene product for the late-onset cardiac form of Fabry disease.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, Tokyo Metropolitan Institute of Medical Science, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ishii
authors.forename: R
authors.initials: R
authors.lastname: Kase
authors.forename: H
authors.initials: H
authors.lastname: Sakuraba
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D017668:Age of Onset; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004795:Enzyme Stability; D000795:Fabry Disease / Q000201:enzymology* / Q000235:genetics*; D005690:Galactose / Q000494:pharmacology; D015870:Gene Expression; D014644:Genetic Variation; D005971:Glutamates; D018698:Glutamic Acid; D005973:Glutamine; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D008553:Melibiose / Q000494:pharmacology; D017354:Point Mutation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D013816:Thermodynamics; D014162:Transfection; D000519:alpha-Galactosidase / Q000235:genetics* / Q000378:metabolism
chemical_list: D005971:Glutamates; D011994:Recombinant Proteins; D005973:Glutamine; D018698:Glutamic Acid; D008553:Melibiose; D000519:alpha-Galactosidase; D005690:Galactose