title: Molecular characterization of two galactosemia mutations and one polymorphism: implications for structure-function analysis of human galactose-1-phosphate uridyltransferase.
abstract: We report here the molecular characterization of two galactosemia mutations, L74P and F171S, and one polymorphism, S135L, in human galactose-1-phosphate uridyltransferase (GALT). Both galactosemia mutations result in reduced enzymatic activity when reconstructed in the cDNA and overexpressed. The polymorphism, in contrast, has near normal activity. Both mutations affect evolutionarily conserved residues, suggesting that they are functionally important, while the polymorphism occurs in a nonconserved domain which is presumably not critical for enzymatic function. The F171S mutation is close to the putative active-site nucleophile. Our data further support the notion of molecular heterogeneity of galactosemia and suggest that galactosemia mutations and GALT polymorphisms may be useful tools in highlighting different functional domains in human GALT.
authors.affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030-3498.
authors.forename: J K
authors.initials: JK
authors.lastname: Reichardt
authors.forename: H L
authors.initials: HL
authors.lastname: Levy
authors.forename: S L
authors.initials: SL
authors.lastname: Woo
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D005693:Galactosemias / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes / Q000737:chemistry; D011110:Polymorphism, Genetic; D015183:Restriction Mapping; D013329:Structure-Activity Relationship; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics* / Q000378:metabolism
chemical_list: D015345:Oligonucleotide Probes; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase