Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sialyltransferases are a family of 10-12 enzymes that catalyze the transfer of sialic acid to carbohydrate groups of glycoproteins and glycolipids. Three sialyltransferase cDNAs have been cloned, revealing a highly conserved sialylmotif in the catalytic domain of these enzymes. Using a polymerase chain reaction-based approach, we cloned a 150-base pair fragment of a new sialymotif from human placenta mRNA, which was then used as a probe to clone the complete coding sequence of the corresponding gene from a cDNA library. Like the other members of the sialyltransferase gene family cloned to date, the new cDNA coded for a protein predicted to have an NH2-terminal signal-anchor sequence and had the sialylmotif located in the center of the molecule. Comparison with the three other cloned sialyltransferases revealed extensive sequence homology that was not recognized earlier. Expression of a soluble recombinant form of the protein in COS-1 cells produced an active sialyltransferase, which used oligosaccharide, glycoprotein, and glycolipid acceptor substrates with terminal galactose in the Gal beta 1,3GalNAc and Gal beta 1, 4GlcNAc sequences but not the Gal beta 1,3GlcNAc sequence. The sialylated products were sensitive to digestion with the Newcastle disease virus sialidase, which is specific for sialic acid-galactose linkages in the alpha 2,3 linkage. The results suggest that this new member of the sialyltransferase gene family is the enzyme previously described as a glycolipid sialyltransferase activity (SAT-3), which forms the terminal sequences NeuAc alpha-2,3Gal beta 1,3GalNAc-R and NeuAc alpha 2,3Gal beta 1, 4GlcNAc-R.
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PMID:Cloning of a novel alpha 2,3-sialyltransferase that sialylates glycoprotein and glycolipid carbohydrate groups. 828 6

Galactosialidosis is an inherited lysosomal storage disease caused by the combined deficiency of lysosomal sialidase and beta-galactosidase secondary to the deficiency of cathepsin A/protective protein, which is associated with sialidase and beta-galactosidase in a high-molecular weight (1.27MDa) complex. Clinical phenotypes of patients as well as the composition of compounds which are stored in patient's tissues implicate sialidase deficiency as the underlying pathogenic defect. The recent cloning and sequencing of lysosomal sialidase [Pshezhetsky, Richard, Michaud, Igdoura, Wang, Elsliger, Qu, Leclerc, Gravel, Dallaire and Potier (1997), Nature Genet. 15, 316-320] allowed us to study the molecular mechanism of sialidase deficiency in galactosialidosis. By Western blotting, using antibodies against the recombinant human enzyme, and by NH2-terminal sequencing, we showed that sialidase is synthesized as a 45.5 kDa precursor and after the cleavage of the 47-amino acid signal peptide and glycosylation becomes a 48.3 kDa mature active enzyme present in the 1.27 kDa complex. Transgenic expression of sialidase in cultured skin fibroblasts from normal controls and from galactosialidosis patients, followed by immunofluorescent and immunoelectron microscopy showed that in both normal and affected cells the expressed sialidase was localized on lysosomal and plasma membranes, but the amount of sialidase found in galactosialidosis cells was approximately 5-fold reduced. Metabolic labelling studies demonstrated that the 48.3 kDa mature active form of sialidase was stable in normal fibroblasts (half-life approximately 2.7 h), whereas in galactosialidosis fibroblasts the enzyme was rapidly converted (half-life approximately 30 min) into 38.7 and 24 kDa catalytically inactive forms. Altogether our data provide evidence that the molecular mechanism of sialidase deficiency in galactosialidosis is associated with abnormal proteolytic cleavage and fast degradation.
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PMID:Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves its rapid degradation. 948 Aug 70

The primary structures of 32 sulfated di-, tri- and tetraantennary N-glycans of human Tamm-Horsfall glycoprotein (THP) have been determined. THP was isolated from the urine of one healthy male donor. The intact carbohydrate chains were released by PNGase-F and fractionated via FPLC on Resource Q, HPLC on LiChrosorb-NH2, and high-pH anion-exchange chromatography on CarboPac PA-1. Characterizations were performed using 500-MHz and 600-MHz 1H-NMR spectroscopy, in combination with sialidase treatments. The type of characterized N-glycans ranged from monosulfated to trisulfated N-glycans, whereby the sulfate groups were present as 3-O-sulfated Gal (Gal3S) and 4-O-sulfated GalNAc (GalNAc4S). A compilation of the established structures is shown below. [structure in text]
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PMID:Sulfated di-, tri- and tetraantennary N-glycans in human Tamm-Horsfall glycoprotein. 976 Jan 89


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