Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lysosomal disorder galactosialidosis is caused by deficiency of the protective protein in the absence of which the activities of the enzymes beta-galactosidase and neuraminidase are reduced. Aside from its protective function towards the two glycosidases, this protein has cathepsin A-like activity. A point mutation in the protective protein gene, resulting in the substitution of Phe412 with Val in the gene product, was identified in two unrelated patients with the late infantile form of the disease. Expression in COS-1 cells of a protective protein cDNA with the base substitution resulted in the synthesis of a mutant protein that lacks cathepsin A-like activity. The newly made mutant precursor was shown to be partially retained in the endoplasmic reticulum. Only a fraction is transported to the lysosomes where it is degraded soon after proteolytic processing into the mature two-chain form. Since the mutant precursor, contrary to the wild type protein, does not form homodimers, the dimerization process might be a condition for the proper targeting and stable conformation of the protective protein. These results clarify the mechanism underlying the combined deficiency in these patients, and give new insight into the structure-function relationship of the wild type protein.
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PMID:A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable. 175 15

1. Two "acid" forms, Am and Al, of beta-galactosidase from sheep kidney have been isolated and purified 349- and 154-fold, respectively, with a recovery of about 8%. 2. Their mol. wts were about 450,000 and 230,000, respectively. Am seems to be a dimer of Al. The aggregation is stimulated by NaCl. 3. The "acid" beta-galactosidase has a pH optimum between 4.0 and 5.0 for both forms. They are located in the lysosomes. The optimal temperature is 37 degrees C and 40 degrees C for Al and Am forms, respectively. 4. Three peaks were detected by isoelectric focusing. After sialidase treatment, these peaks were obtained at higher pH values. 5. The activation energy values were 10.75 and 11.72 kcal/mol for Am and Al, respectively. 6. A variety of chemicals were tested as possible activators or inhibitors. The enzyme is strongly inhibited by gamma-D-galactonolactone, and the kinetic evidence suggests a competitive inhibition in all cases.
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PMID:Purification and characterization of different "acid" beta-galactosidases from sheep kidney. 176 16

Sialic acid-containing carbohydrates were isolated from sialidosis urine by a combination of gel-filtration on Bio-Gel P-6 and medium-pressure anion-exchange chromatography on Mono Q. The Mono Q fractions were subjected to 500-MHz 1H-NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb-NH2. These methods indicated the presence of various N-acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. Among the structures were fully and partially sialylated mono-, di-, tri- and tetra-antennary compounds. A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. Sialidosis urinary oligosaccharides contained relatively more alpha 2-6 linked sialic acid than oligosaccharides from galactosialidosis urine. It could be concluded that the additional beta-galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis.
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PMID:A comparative study of sialyloligosaccharides isolated from sialidosis and galactosialidosis urine. 177 19

Ovine GM1 gangliosidosis, an inherited disease of sheep with deficiencies of beta-galactosidase and alpha-neuraminidase, storage of GM1 ganglioside, asialo-GM1 and neutral long chain oligosaccharides in the brain, autosomal recessive inheritance, and histopathologic lesions typical of lysosomal storage diseases, has been described recently. Selected tissues from two sheep with the condition and an age-matched control were examined by transmission electron microscopy to characterize the ultrastructural lesions. In all central and peripheral neurons, the majority of the cytoplasmic space was occupied by membrane-limited enlarged bodies judged to be lysosomes, with a resultant displacement of normal organelles. The neuronal lysosomes usually contained stacks and concentric whorls of lamellae of stored material with a periodicity of 25 to 75 nM. Individual lamellae consisted of fine, multilayered (three to 10, and occasionally more) bands. Less commonly, enlarged neuronal lysosomes contained fibrillogranular or electron dense material. Central nervous system microglia and peripheral nervous system satellite cells had less extensive storage of similar material within enlarged lysosomes, whereas oligodendrocytes, astrocytes, and Schwann cells were relatively unaffected. Hepatocytes and renal epithelial cells also had storage of less quantity than neurons, but within even larger lysosomes. In contrast to neuronal storage material, visceral storage consisted of vesicles containing fibrillogranular or electron dense material within a mostly electron lucent matrix with only occasional lamellae. Kupffer cells and macrophages from bone marrow were affected similarly to but less severely than hepatocytes and renal epithelial cells, whereas hematopoietic cells and chondrocytes were unaffected. Both neuronal and visceral storage were evident, but the neuronal storage was much more extensive.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ultrastructural lesions of ovine GM1 gangliosidosis. 178 67

Bacteroides fragilis NCDO 2217 produced a wide range of cell-associated hydrolytic enzymes (neuraminidase, alpha-fucosidase, alpha-N-acetylgalactosaminidase, beta-galactosidase, beta-N-acetylglucosaminidase) that could potentially degrade the carbohydrate moieties of mucin, a complex glycoprotein. The type of substrate used for growth markedly influenced their formation in batch cultures. Synthesis of neuraminidase, alpha-fucosidase, alpha-N-acetylgalactosaminidase and to a lesser extent, beta-N-acetylglucosaminidase, was inversely related to growth rate in continuous cultures (D = 0.03 h-1-0.23 h-1) in which porcine gastric mucin provided the sole source of carbon and nitrogen.
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PMID:Formation of glycoprotein degrading enzymes by Bacteroides fragilis. 190 53

Mono- and oligosaccharides, each containing a reducing end group, were labeled with the charged fluorophore 8-aminonaphthalene-1,3,6-trisulphonic acid and the resulting derivatives were separated with high resolution by polyacrylamide gel electrophoresis using a method developed recently (P. Jackson, Biochem. J. 1990, 270, 705-713) but with an alternative electrophoretic buffer system. The fluorescent derivatives of glucose and all its straight chain, alpha 1-4 linked, oligomers from maltose to maltoheptaose were well resolved. Various isomers such as maltose and lactose could be separated, as were maltose and cellobiose and some epimers, for instance glucose and galactose. The method was applied to the analysis of the partial sequential degradation of a complex oligosaccharide with neuraminidase and beta-galactosidase. Gels showing fluorescent saccharide band patterns were recorded in picomolar quantities either photographically or using an imaging system based on a cooled charge-coupled device.
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PMID:Polyacrylamide gel electrophoresis of reducing saccharides labeled with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonic acid: application to the enzymological structural analysis of oligosaccharides. 190 15

Sialidase isolated from human placenta is associated with several proteins including acid beta-galactosidase, carboxypeptidase, N-acetyl-alpha-galactosaminidase, and others. These proteins are thought to form an aggregated complex during isolation of sialidase. One of the proteins of 60 kDa was recently identified by Potier et al. (Biochem. Biophys. Res. Comm. 173, 449-456, 1990) as a sialidase protein: this protein also cross-reacted with anti-prosaposin antibodies. We have isolated this protein and from the following evidence identified it as a heavy chain component of immunoglobulin G and not sialidase or a derivative of prosaposin. On gel filtration HPLC, sialidase activity and the 60 kDa protein were clearly separated from one another. The 60 kDa protein cross-reacted not only with antibodies raised against human saposins A, C, and D, but also with second antibody (goat anti-rabbit immunoglobulin G antibody) alone. This 60 kDa protein strongly cross-reacted with anti-human immunoglobulin G antibodies. The sequence of the initial 15 amino acids from the N-terminus of the 60 kDa protein was identical to the sequence of an immunoglobulin G heavy chain protein Tie (gamma 1).
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PMID:Human placental sialidase complex: characterization of the 60 kDa protein that cross-reacts with anti-saposin antibodies. 190 36

The protective protein was first discovered because of its deficiency in the metabolic storage disorder galactosialidosis. It associates with lysosomal beta-galactosidase and neuraminidase, toward which it exerts a protective function necessary for their stability and activity. Human and mouse protective proteins are homologous to yeast and plant serine carboxypeptidases. Here, we provide evidence that this protein has enzymatic activity similar to that of lysosomal cathepsin A: 1) overexpression of human and mouse protective proteins in COS-1 cells induces a 3-4-fold increase of cathepsin A-like activity; 2) this activity is reduced to approximately 1% in three galactosialidosis patients with different clinical phenotypes; 3) monospecific antibodies raised against human protective protein precipitate virtually all cathepsin A-like activity in normal human fibroblast extracts. Mutagenesis of the serine and histidine active site residues abolishes the enzymatic activity of the respective mutant protective proteins. These mutants, however, behave as the wild-type protein with regard to intracellular routing, processing, and secretion. In contrast, modification of the very conserved Cys60 residue interferes with the correct folding of the precursor polypeptide and, hence, its intracellular transport and processing. The secreted active site mutant precursors, endocytosed by galactosialidosis fibroblasts, restore beta-galactosidase and neuraminidase activities as effectively as wild-type protective protein. These findings indicate that the catalytic activity and protective function of the protective protein are distinct.
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PMID:Human lysosomal protective protein has cathepsin A-like activity distinct from its protective function. 190 82

A brief (30 min) treatment of mouse peritoneal cells (mixture of nonadherent lymphocytes and adherent macrophages) with 1-20 micrograms of lysophosphatidylcholine (lyso-PC) per ml in serum-supplemented RPMI medium 1640, followed by a 3-hr cultivation of the adherent cells alone, results in a greatly enhanced Fc receptor-mediated phagocytic activity of macrophages. This rapid process of macrophage activation was found to require a serum factor, the vitamin D3 binding protein (the human protein is known as group-specific component; Gc). Efficient activation of macrophages was achieved by using medium containing purified human Gc protein. Analysis of intercellular signal transmission among nonadherent (B and T) cells revealed that lyso-PC-treated B cells modify Gc protein to yield a proactivating factor, which can be converted by T cells to the macrophage-activating factor. This rapid generation process of the macrophage-activating factor was also demonstrated by stepwise incubation of Gc protein with lyso-PC-treated B-cell ghosts and untreated T-cell ghosts, suggesting that Gc protein is modified by preexisting membranous enzymes to yield the macrophage-activating factor. Incubation of Gc protein with a mixture of beta-galactosidase and sialidase efficiently generated the macrophage-activating factor. Stepwise incubation of Gc protein with B- or T-cell ghosts and sialidase or beta-galactosidase revealed that Gc protein is modified by beta-galactosidase of B cells and sialidase of T cells to yield the macrophage-activating factor. Administration to mice of a minute amount (4-10 pg per mouse) of in vitro, enzymatically generated macrophage-activating factor resulted in a greatly enhanced (3- to 7-fold) ingestion activity of macrophages.
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PMID:Vitamin D3 binding protein (group-specific component) is a precursor for the macrophage-activating signal factor from lysophosphatidylcholine-treated lymphocytes. 192 12

1. The sialidase purified from the hepatopancreas of Penaeus japonicus is able to bind the acidic beta-galactosidase in vitro. No protective protein, Mr 32,000, was detected in either purified enzyme preparation. 2. The specific activity of the isolated sialidase is 55.0 mU/mg of protein. After polyacrylamide gel electrophoresis under denaturing conditions, the purified shrimp enzyme was found to consist of monomers of Mr 32,000. 3. The sialidase from shrimp has an isoelectric point (pI) of 4.6 +/- 0.1. 4. The shrimp enzyme has the pH optimum at 5.0 and its Km was 5.5 microM with 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid as substrate. The enzyme activity was inhibited by either Hg2+ or Cu2+ ions.
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PMID:A sialidase from the hepatopancreas of the shrimp Penaeus japonicus (Crustacea: Decapoda): reversible binding with the acidic beta-galactosidase. 198 76


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