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