Journal of Biological Chemistry
Volume 287, Issue 3, 13 January 2012, Pages 1801-1812
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Protein Structure and Folding
Crystal Structure of Human β-Galactosidase: STRUCTURAL BASIS OF GM1 GANGLIOSIDOSIS AND MORQUIO B DISEASES*

https://doi.org/10.1074/jbc.M111.293795Get rights and content
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GM1 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, GM1 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.

Crystal Structure
Glycoprotein
Lysosomal Storage Disease
Structural Biology
X-ray Crystallography
Galactosidase

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The atomic coordinates and structure factors (codes 3THC and 3THD) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

*

This work was supported in part by the Targeted Proteins Research Program and by grants-in-aid for Scientific Research from Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan (to U. O., Y. S., and T. S.).

This article contains supplemental Table S1.

1

Both authors contributed equally to this work.