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:3.1.6.1 (sulfatase)
3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 6-sulfatase specific for sugasr of the galactose configuration was purified 81-fold from the crude extract of Actinobacillus sp. IFO-13310. This preparation contained activity towards both N-acetylgalactosamine 6-sulfate and galactose 6-sulfate (relative activity, 2.4 : 1). The enzyme also release inorganic sulfate from the non-reducing galactose 6-sulfate end group of a trisaccharide disulfate prepared from keratan sulfate by sequential degradation with endo-beta-galactosidase, N-acetylglucosamine-6-sulfatase and exo-beta-N-acetylglucosaminidase. In addition, a tetrasaccharide trisulfate bearing the non-reducing N-acetylglucosamine 6-sulfate end group, also enzymatically prepared from keratan sulfate, was degraded to give rise to inorganic sulfate, N-acetylglucosamine and galactose by the sequential action of this enzyme, N-acetylglucosamine-6-sulfatase, exo-beta-N-acetylglucosaminidase and exo-beta-galactosidase (Charonia lampas).
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PMID:Galactose-6-sulfatase from Actinobacillus sp. IFO-13310 and its action on sulfated oligosaccharides from keratan sulfate. 15 51

Fibroblasts of four patients affected with mucosulfatidosis (multiple sulfatase deficiency, Austin variant of metachromatic leukodystrophy) were assayed for activities of the five sulfatases known to degrade mucopolysaccharides. These were iduronide 2-sulfate sulfatase, sulfamidase, N-acetyl-galactosamine 6-sulfate sulfatase, arylsulfatase B (N-acetylgalactosamine 4-sulfate sulfatase), and N-acetylglucosamine 6-sulfate sulfatase. The activities of these five sulfatases were severely depressed, thus confirming the known deficiency of arylsulfatase B and the absence of the Hunter and Sanfilippo III A corrective factors that have iduronide 2-sulfate sulfatase and sulfamidase activity, respectively. Together with earlier reports of the deficiencies of arylsulfatases A and C, cholesteryl sulfatase, and dehydroepiandrosterone sulfatae, mucosulfatidosis is now characterized by the deficiency of nine different sulfatases.
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PMID:Multiple deficiency of mucopolysaccharide sulfatases in mucosulfatidosis. 52 91

N-Acetylglucosamine-6-sulfatase activity was assayed by incubation of the radiolabeled disaccharide O-(a-N-acetylglucosamine-6-sulfate)-(1----3)-L-[6-3H]-idonic acid (GlcNAc6S-IdOA), with homogenates of leucocytes, cultured fibroblasts, and urine from normal individuals, patients affected with N-acetylglucosamine-6-sulfatase-deficiency (Sanfilippo D syndrome, mucopolysaccharidosis type IIID), and patients affected with other mucopolysaccharidoses and lysosomal storage disorders. The assay clearly distinguished affected homozygotes from their obligate heterozygotes and normal controls and other lysosomal storage disorders. Sulfatase activity in fibroblasts, leucocytes, and urine toward GlcNAc6S-IdOA exhibited a pH optimum at 4.2, 4.5, and 5.1, respectively. Sulfatase activity in fibroblasts had an apparent Km of 7.2 microM and was significantly inhibited by both sulfate and phosphate ions. The action of fibroblast or leucocyte N-acetylglucosamine-6-sulfatase activity toward GlcNAc6S-IdOA is recommended for the routine enzymatic detection and classification of mucopolysaccharidosis type IIID patients.
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PMID:Sanfilippo D syndrome: estimation of N-acetylglucosamine-6-sulfatase activity with a radiolabeled monosulfated disaccharide substrate. 250 Aug 66

Various sulfatase activities were assayed in cultured skin fibroblasts from patients with multiple sulfatase deficiency (MSD). MSD cell lines displayed deficiencies of arylsulfatase A and iduronate sulfatase, but activities of arylsulfatase B, N-acetylgalactosamine 6-sulfate sulfatase and N-acetylglucosamine 6-sulfate sulfatase were within normal ranges, but not consistently. Arylsulfatase A, minor anionic arylsulfatase and N-acetylgalactosamine 6-sulfate sulfatase in MSD cell lines had similar Km, pH optima, inhibitory or activator sensitivity to that of normal skin fibroblasts. Arylsulfatase B in MSD cell lines also had properties similar to that of normal skin fibroblasts, except an abnormal heat stability. From our results, we conclude that properties of arylsulfatase A, minor anionic arylsulfatase and N-acetylgalactosamine 6-sulfate sulfatase in MSD fibroblasts were intact. On the other hand, arylsulfatase B in MSD might be a functionally abnormal enzyme.
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PMID:Properties of sulfatases in cultured skin fibroblasts of multiple sulfatase deficient patients. 733 23

N-Acetylglucosamine-6-sulfate sulfatase (NG6SS) is an enzyme that catalyzes the hydrolysis of sulfate esters from the C-6 hydroxyl of N-acetylglucosamine. We report our purification and characterization of the enzyme and the discovery that it can remove sulfate from internally sulfated GlcNAc on glycopeptides and glycoproteins. The enzyme was purified from bovine kidney over 200,000-fold using a combination of ion-exchange and size-exclusion chromatography. NG6SS is soluble and occurs as a single subunit with apparent solution molecular weight of 60.2 kDa on gel filtration chromatography and approximately 52.5 and 57.8 kDa on reducing and nonreducing SDS/PAGE, respectively. The enzyme is highly basic and exhibits a broad pH range with an optimum at pH 6.5 and a temperature optimum of 37 degrees C. Among the mono- and disaccharide sulfates tested, only GlcNAc-6-SO4 is an effective substrate with a Km of 4.7 mM, and either free sulfate or phosphate inhibits the activity. Unexpectedly, we found that the enzyme displays endosulfatase activity and quantitatively releases 35SO4 from 35SO4-labeled glycopeptides and intact glycoproteins isolated from human Molt-3 cells, which we have previously shown to synthesize glycoproteins containing GlcNAc-6-SO4 residues within the sequence Gal beta 1-4[SO-3-6]-GlcNAc beta 1-R of complex-type N-linked oligosaccharides. The N-terminal sequence of the bovine NG6SS was homologous to a human-liver-derived N-acetylglucosamine-6-sulfatase. The endosulfatase activity of bovine kidney NG6SS may be important in its potential role in the degradation of sulfated glycans and may make this enzyme a valuable reagent to study the biological functions of sulfated glycoproteins.
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PMID:Purification and characterization of N-acetylglucosamine-6-sulfate sulfatase from bovine kidney: evidence for the presence of a novel endosulfatase activity. 815 45

Mucopolysaccharidosis type IIID (MPS IIID) is a lysosomal storage disorder resulting from lack of activity of the lysosomal hydrolase N-acetylglucosamine 6-sulfatase (6S) (EC 3.1.6.14). The syndrome is associated with systemic and central nervous system (CNS) heparan sulfate glycosaminoglycan (HS-GAG) accumulation, secondary storage of lipids, and severe, progressive dementia. In this investigation, caprine MPS IIID, established as a large animal model for the human disease, was used to evaluate the efficacy of enzyme replacement therapy (ERT). Recombinant caprine 6S (rc6S) (1 mg/kg/dose) was administered intravenously to one MPS IIID goat kid at 2, 3, and 4 wks of age. Five days after the last dose, the uronic acid (UA) content and the composition of uncatabolized HS-GAG fractions in the brain of the ERT-treated MPS IIID kid were similar to those from a control, untreated MPS IIID animal. However, hepatic uronic acid levels in the treated MPS IIID kid were approximately 90% lower than those in the untreated MPS IIID control; whereas the composition of the residual hepatic HS-GAG was identical to that in the untreated animal. Marked reduction of lysosomal storage vacuoles in hepatic cells of the treated MPS IIID kid was observed, but ERT had no effect on CNS lesions. No residual 6S activity was detected in brain or liver. This preliminary investigation indicates that other treatment regimens will be necessary to ameliorate MPS III-related CNS lesions.
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PMID:Caprine mucopolysaccharidosis IIID: a preliminary trial of enzyme replacement therapy. 1130 88

During fasting of animals, there is decreased content of skin glycosaminoglycans (GAGs) accompanied by decrease in their biosynthesis. Since tissue GAG content depends on both synthesis and degradation of these molecules, we asked whether fasting affects the activity of several tissue glycosidases. Therefore we measured the activity of skin neutral and acidic endoglycosidases, some exoglycosidases: beta-N-acetylhexosaminidase [EC 3.2.1.30], beta-galactosidase [EC 2.1.23], beta-glucuronidase [EC 3.2.1.31], alpha-iduronidase [EC 3.2.1.76], and two sulfatases: arylsulfatase B [EC 3.1.6.1] and 6-sulfatase [EC 3.1.6.14] in the skin of control and fasted rats. Although fasting was accompanied by distinct decrease in the activity of most neutral endoglycosidases, no characteristic changes in the activity of exoglycosidases were found. In contrast, we found that fasting is associated with increase in the activity of acidic endoglycosidases (of lysosomal origin) which degraded hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate and heparin. The same GAGs were decreased in the skin of fasted rats. Our data suggest that the phenomenon is a result of increased intracellular degradation of these molecules. Therefore, not only decreased biosynthesis of GAGs during fasting, but also increased their intracellular degradation may contribute to decrease in GAG skin content.
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PMID:Glycosaminoglycan-degrading enzymes in the skin of fasted rats. 1195 38

Mucopolysaccharidosis IIID (MPS IIID) is a lysosomal storage disease associated with deficient activity of the enzyme N-acetylglucosamine 6-sulfatase (EC 3.1.6.14), a lysosomal hydrolase in the heparan sulfate glycosaminoglycan (HS-GAG) degradation pathway. In caprine MPS IIID, enzyme replacement therapy reversed early postnatal systemic but not primary or secondary central nervous system (CNS) substrate accumulations. The caprine MPS IIID large animal model system was used in this investigation to define the developmental profile of morphological and biochemical perturbations to estimate a time frame for therapeutic intervention. Light and electron microscopy were used to compare the CNS, liver, and kidney of normal +/+, MPS IIID carrier +/-, and MPS IIID-affected -/- goat kids (kids), at 60, 113-114, 128-129, and 135 d gestation (dg) of a 150-d gestational period, at birth, and at 59-64 d of postnatal (d-pn) age. In the CNS of -/- kids, morphological correlations of HS-GAG and glycolipid accumulations were evident in early differentiating neurons at 60 dg. CNS and systemic developmental, regional, and cellular differences in -/- kids at all time points included more prominent and earlier accumulation of lucent, putative HS-GAG substrates in lysosomes of meningeal and perivascular macrophages and hepatic sinusoidal cells than in CNS, hepatic, or renal parenchymal cells. The amounts and compositions of HS-GAG substrates in the brain and liver of +/+, +/-, and -/- kids were determined at 60, 65, 113-114, and 128-135 dg, at birth, and 53-78 d-pn. In the CNS of -/- kids, HS-GAG concentrations were variable and exceeded those of age-matched control tissue samples in the third but not the second trimester. In contrast, hepatic HS-GAG levels in -/- kids exceeded control values at all time points evaluated and paralleled the progressive morphological alterations. CNS and hepatic HS-GAG compositions in -/- kids were similar to each other and were more complex at all pre- and postnatal ages than those from control kids. Based on the time frame of development of CNS lesions and biochemical perturbations, prenatal therapeutic intervention in caprine MPS IIID is likely to be necessary to prevent or ameliorate substantive CNS and systemic lesions.
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PMID:Caprine mucopolysaccharidosis IIID: fetal and neonatal brain and liver glycosaminoglycan and morphological perturbations. 1545 41

Sanfilippo Syndrome or Mucopolysaccharidosis Ill (MPS Ill) is a group of lysosomal storage diseases resulting from a deficiency of one of four lysosomal enzymes: Type A - heparan N-sulfatase (SGSH), Type B - a-N-acetylglucosaminidase (NAGLU), Type C - acetyl CoA a-glucosaminide acetyltransferase (HGSNAT) and Type D - N-acetylglucosamine-6-sulfatase (GNS). Each of these enzymes is necessary for degradation of heparan sulfate. Deficiency of any of these enzymes manifests as a neurodegenerative disorder with accompanying somatic manifestations. Typically this presents early in life with developmental delays followed by developmental regression and usually results in death sometime during the second decade of life, though several less severe cases have been described living into late adulthood (30's to 60's). Often there is a delay of several years from time of symptom onset to diagnosis. Currently treatment is limited to supportive care. We will briefly discuss the typical natural history and presumed pathophysiology of the disease. We will also discuss current experimental therapies being pursued for treatment of this devastating disease. These include enzyme replacement, gene therapy, stem cell therapy, and substrate reduction approaches.
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PMID:Mucopolysaccharidosis III (Sanfilippo Syndrome)- disease presentation and experimental therapies. 2534 95

Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is a lysosomal storage disease in which heparan sulfate is accumulated in lysosomes, as well as outside of cells, as the primary storage material. This disease is a complex of four conditions caused by dysfunctions of one of genes coding for lysosomal enzymes involved in degradation of heparan sulfate: SGSH (coding for heparan N-sulfatase) - causing MPS IIIA, NAGLU (coding for alpha-N-acetylglucosaminidase) - causing MPS IIIB, HGSNAT (coding for acetyl CoA alpha-glucosaminide acetyltransferase) - causing MPS IIIC), and GNS (coding for N-acetylglucosamine-6-sulfatase) - causing MPS IIID. The primary storage is responsible for some disease symptoms, but other arise as a result of secondary storage, including glycosphingolipids, and subsequent processes, like oxidative stress and neuroinflammation. Central nervous system is predominantly affected in all subtypes of MPS III. Heparan sulfate and its derivatives are the most commonly used biomarkers for diagnosis and prediction procedures. Currently, there is no therapy for Sanfilippo syndrome, however, clinical trials are ongoing for enzyme replacement therapy, gene therapy and substrate reduction therapy (particularly gene expression-targeted isoflavone therapy).
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PMID:Glycosaminoglycans and mucopolysaccharidosis type III. 2710 May 13


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