title: Structural bases of GM1 gangliosidosis and Morquio B disease.
abstract: Allelic mutations of the lysosomal beta-galactosidase gene cause heterogeneous clinical phenotypes, such as GM1 gangliosidosis and Morquio B disease, the former being further classified into three variants, namely infantile, juvenile and adult forms; and heterogeneous biochemical phenotypes were shown in these forms. We tried to elucidate the bases of these diseases from a structural viewpoint. We first constructed a three-dimensional structural model of human beta-galactosidase by means of homology modeling. The human beta-galactosidase consists of three domains, such as, a TIM barrel fold domain, which functions as a catalytic domain, and two galactose-binding domain-like fold domains. We then constructed structural models of representative mutant beta-galactosidase proteins (G123R, R201C, I51T and Y83H) and predicted the structural change associated with each phenotype by calculating the number of affected atoms, determining the root-mean-square deviation and the solvent-accessible surface area, and by color imaging. The results show that there is a good correlation between the structural changes caused by amino-acid substitutions in the beta-galactosidase molecule, as well as biochemical and clinical phenotypes in these representative cases. Protein structural study is useful for elucidating the bases of these diseases.
authors: Agricultural Bioinformatics Research Unit, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors: Mizuki
authors: M
authors: Morita
authors: Seiji
authors: S
authors: Saito
authors: Kazuyoshi
authors: K
authors: Ikeda
authors: Kazuki
authors: K
authors: Ohno
authors: Kanako
authors: K
authors: Sugawara
authors: Toshihiro
authors: T
authors: Suzuki
authors: Tadayasu
authors: T
authors: Togawa
authors: Hitoshi
authors: H
authors: Sakuraba
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D016537:Gangliosidosis, GM1 / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009085:Mucopolysaccharidosis IV / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D001616:beta-Galactosidase / Q000737:chemistry* / Q000235:genetics*
chemical_list: D001616:beta-Galactosidase