3thd | pdb_00003thd

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

spinqualitylabelsall models 3thd, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3thd is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.79Å Ligands: CL, DGJ, EDO, NAG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease BGAL_HUMAN GM1 gangliosidosis type 2;Mucopolysaccharidosis type 4B;GM1 gangliosidosis type 1;GM1 gangliosidosis type 3. GM1-gangliosidosis 1 (GM1G1) [MIM:230500: An autosomal recessive lysosomal storage disease marked by the accumulation of GM1 gangliosides, glycoproteins and keratan sulfate primarily in neurons of the central nervous system. GM1-gangliosidosis type 1 is characterized by onset within the first three months of life, central nervous system degeneration, coarse facial features, hepatosplenomegaly, skeletal dysmorphology reminiscent of Hurler syndrome, and rapidly progressive psychomotor deterioration. Urinary oligosaccharide levels are high. It leads to death usually between the first and second year of life. Note=The disease is caused by mutations affecting the gene represented in this entry. GM1-gangliosidosis 2 (GM1G2) [MIM:230600: A gangliosidosis characterized by onset between ages 1 and 5. The main symptom is locomotor ataxia, ultimately leading to a state of decerebration with epileptic seizures. Patients do not display the skeletal changes associated with the infantile form, but they nonetheless excrete elevated amounts of beta-linked galactose-terminal oligosaccharides. Inheritance is autosomal recessive. Note=The disease is caused by mutations affecting the gene represented in this entry. GM1-gangliosidosis 3 (GM1G3) [MIM:230650: A gangliosidosis with a variable phenotype. Patients show mild skeletal abnormalities, dysarthria, gait disturbance, dystonia and visual impairment. Visceromegaly is absent. Intellectual deficit can initially be mild or absent but progresses over time. Inheritance is autosomal recessive. Note=The disease is caused by mutations affecting the gene represented in this entry. Mucopolysaccharidosis 4B (MPS4B) [MIM:253010: A form of mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life. Note=The disease is caused by mutations affecting the gene represented in this entry. Function BGAL_HUMAN Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans. Isoform 2 has no beta-galactosidase catalytic activity, but plays functional roles in the formation of extracellular elastic fibers (elastogenesis) and in the development of connective tissue. Seems to be identical to the elastin-binding protein (EBP), a major component of the non-integrin cell surface receptor expressed on fibroblasts, smooth muscle cells, chondroblasts, leukocytes, and certain cancer cell types. In elastin producing cells, associates with tropoelastin intracellularly and functions as a recycling molecular chaperone which facilitates the secretions of tropoelastin and its assembly into elastic fibers. Publication Abstract from PubMed 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. Crystal structure of human beta-galactosidase: structural basis of Gm1 gangliosidosis and morquio B diseases.,Ohto U, Usui K, Ochi T, Yuki K, Satow Y, Shimizu T J Biol Chem. 2012 Jan 13;287(3):1801-12. doi: 10.1074/jbc.M111.293795. Epub 2011 , Nov 28. PMID:22128166 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Galactosidase 3D structures

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