Crystal structure of human β-galactosidase: structural basis of Gm1 gangliosidosis and morquio B diseases.

[gm1 gangliosidosis]

G (M 1 ) 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 (M 1 ) 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 .