3THD

Crystal structure of human beta-galactosidase in complex with 1-deoxygalactonojirimycin

Summary for 3THD

• Entry DOI: 10.2210/pdb3thd/pdb
• Related: 3THC
• Descriptor: Beta-galactosidase, 2-acetamido-2-deoxy-beta-D-glucopyranose, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: beta-galactosidase, tim-barrel domain, glycosyl hydrolase, glycosylation, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Lysosome. Isoform 2: Cytoplasm, perinuclear region: P16278
• Total number of polymer chains: 4
• Total formula weight: 300260.22

Authors

Ohto, U.,Shimizu, T. (deposition date: 2011-08-18, release date: 2011-12-07, Last modification date: 2024-11-13)

Primary citation

Ohto, U.,Usui, K.,Ochi, T.,Yuki, K.,Satow, Y.,Shimizu, T.
Crystal structure of human beta-galactosidase: structural basis of Gm1 gangliosidosis and morquio B diseases
J.Biol.Chem., 287:1801-1812, 2012

PubMed 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.

PubMed: 22128166
DOI: 10.1074/jbc.M111.293795

Experimental method

X-RAY DIFFRACTION (1.79 Å)