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

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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. 2012 Jan 13;287(3):1801-12. doi: 10.1074/jbc.M111.293795. Epub 2011 Nov 28.

PubMed ID
22128166 [ View in 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 beta-d-galactosidase (beta-Gal), which lead to accumulations of the beta-Gal substrates, G(M1) ganglioside, and keratan sulfate. beta-Gal is an exoglycosidase that catalyzes the hydrolysis of terminal beta-linked galactose residues. This study shows the crystal structures of human beta-Gal in complex with its catalytic product galactose or with its inhibitor 1-deoxygalactonojirimycin. Human beta-Gal is composed of a catalytic TIM barrel domain followed by beta-domain 1 and beta-domain 2. To gain structural insight into the molecular defects of beta-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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Beta-galactosidaseP16278Details