title: Crystal structure of human β-galactosidase: structural basis of Gm1 gangliosidosis and morquio B diseases.
abstract: G(M1) gangliosidosis and Morquio B are autosomal recessive lysosomal storage diseases associated with a neurodegenerative disorder or dwarfism and skeletal abnormalities, respectively. These diseases are caused by deficiencies in the lysosomal enzyme β-d-galactosidase (β-Gal), which lead to accumulations of the β-Gal substrates, G(M1) ganglioside, and keratan sulfate. β-Gal is an exoglycosidase that catalyzes the hydrolysis of terminal β-linked galactose residues. This study shows the crystal structures of human β-Gal in complex with its catalytic product galactose or with its inhibitor 1-deoxygalactonojirimycin. Human β-Gal is composed of a catalytic TIM barrel domain followed by β-domain 1 and β-domain 2. To gain structural insight into the molecular defects of β-Gal in the above diseases, the disease-causing mutations were mapped onto the three-dimensional structure. Finally, the possible causes of the diseases are discussed.
authors: From the Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Umeharu
authors: U
authors: Ohto
authors: Kimihito
authors: K
authors: Usui
authors: Toshinari
authors: T
authors: Ochi
authors: Kenjiro
authors: K
authors: Yuki
authors: Yoshinori
authors: Y
authors: Satow
authors: Toshiyuki
authors: T
authors: Shimizu
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000737:chemistry; D018360:Crystallography, X-Ray; D005677:G(M1) Ganglioside / Q000235:genetics / Q000378:metabolism; D005690:Galactose / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016537:Gangliosidosis, GM1 / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D006868:Hydrolysis; D007632:Keratan Sulfate / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D009085:Mucopolysaccharidosis IV / Q000201:enzymology* / Q000235:genetics; D009154:Mutation; D017434:Protein Structure, Tertiary; D001616:beta-Galactosidase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D017485:1-Deoxynojirimycin; D005677:G(M1) Ganglioside; D007632:Keratan Sulfate; C090092:migalastat; D001616:beta-Galactosidase; D005690:Galactose