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2-deoxy-2-sulfamido-D-glucose + H2O
2-deoxy-2-amino-D-glucose + sulfate
-
-
-
-
ir
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
glucosamine 2,6-disulfate + H2O
D-glucosamine 6-sulfate + sulfate
heparan sulfate + H2O
?
-
-
-
?
heparan sulfate + H2O
? + sulfate
heparin + H2O
? + sulfate
N-sulfo-D-glucosamine + H2O
D-glucosamine + sulfate
-
-
-
-
ir
O-(alpha-2-sulfamino-2-deoxy-D-glucopyranosyl)-(1-3)-L-idonic acid
O-(alpha-2-amino-2-deoxy-D-glucopyranosyl)-(1-3)-L-idonic acid + sulfate
-
-
-
-
?
tetrasaccharides + H2O
?
-
-
-
-
?
additional information
?
-
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
-
-
-
?
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
-
-
-
-
?
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
-
-
-
-
?
glucosamine 2,6-disulfate + H2O
D-glucosamine 6-sulfate + sulfate
-
-
-
-
ir
glucosamine 2,6-disulfate + H2O
D-glucosamine 6-sulfate + sulfate
-
no activity with purified enzyme
-
-
?
heparan sulfate + H2O
? + sulfate
-
-
-
-
?
heparan sulfate + H2O
? + sulfate
-
-
-
-
ir
heparan sulfate + H2O
? + sulfate
-
-
-
?
heparan sulfate + H2O
? + sulfate
-
degradation of heparan sulfate
-
-
?
heparan sulfate + H2O
? + sulfate
-
-
-
-
?
heparan sulfate + H2O
? + sulfate
-
-
-
-
?
heparin + H2O
? + sulfate
-
-
-
-
?
heparin + H2O
? + sulfate
-
-
-
-
ir
heparin + H2O
? + sulfate
-
degradation products of
-
-
?
heparin + H2O
? + sulfate
-
-
-
-
?, ir
additional information
?
-
-
overview: effect of aglycone structure
-
-
?
additional information
?
-
-
enzyme defiency leads to defective lysosomal degradation of the glycosaminoglycan heparan sulfate, mutations of the enzyme are responsible for mucopolysaccharidosis type IIIA, i.e. Sanfilippo A syndrome, onset and progression of the disease, overview
-
-
?
additional information
?
-
-
reduced activity of sulfamidase results in intracellular accumulation of heparan sulfate, with the brain the primary site of pathology, e.g. in mucopolysaccharidosis type IIIA, or Sanfilippo syndrome, an inherited neurodegenerative lysosomal storage disorder, progressive loss of learned skills, sleep disturbance and behavioural problems occur. A potential therapy method is the repeated injection of the enzyme into cerebrospinal fluid via cisterna magna leading to a reduction of the number of lysosomal storage inclusions in the brain with a significant decrease in the immunohistochemical staining of a lysosomal membrane marker, and to reduced numbers of activated isolectin-B4-positive microglia and GFAP-positive astrocytes in some brain regions, phenotype, mouse model, overview
-
-
?
additional information
?
-
-
repeated human enzyme injection into murine cerebrospinal fluid via cisterna magna leads to a reduction of heparan sulfate-derived monosulfated disaccharide in the brain and spinal cord, reduced lysosomal vesicle formation in various cell types, reduced axonal spheroids, and improved behaviour of treated mice, mouse model, overview
-
-
?
additional information
?
-
the enzymatic activity of the enzyme is measured in a two-step reaction: 4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide is desulfated by the enzyme to become a substrate for alpha-glucosidase, which converts 4-methylumbelliferyl-alpha-D-N-sulfoglucosamine to methylumbelliferone, which is a fluorescent compound
-
-
?
additional information
?
-
-
congenital deficiency of sulfamidase leads to mucopolysaccharidosis type IIIA or Sanfilippo syndrome, a lysosomal storage disorder, with consequent accumulation of partially degraded heparan sulfate in lysosomes and the central nervous system as the predominant site of tissue damage, overview
-
-
?
additional information
?
-
-
the enzymatic activity of the enzyme is measured in a two-step reaction: 4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide is desulfated by the enzyme to become a substrate for alpha-glucosidase from Bacillus stearothermophilus, which converts 4-methylumbelliferyl-alpha-D-N-sulfoglucosamine to methylumbelliferone, which is a fluorescent compound. Method evaluation
-
-
?
additional information
?
-
-
the enzymatic activity of the enzyme is measured in a two-step reaction: 4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide is desulfated by the enzyme to become a substrate for alpha-glucosidase from Bacillus stearothermophilus, which converts 4-methylumbelliferyl-alpha-D-N-sulfoglucosamine to methylumbelliferone, which is a fluorescent compound. Method evaluation
-
-
?
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evolution
despite the low sequence identity between the unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. A highly conserved lysine in O-sulfatases is replaced in the N-sulfoglucosamine sulfohydrolase by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate
additional information
the enzyme shows low structural flexibility. The consensus active site lies in domain 1 in a narrow pocket at the bottom of a surface cleft and close to the end of the first beta-strand, active site structure, overview. Proposed interactions between the terminal N-sulfoglucosamine residue of the substrate with the enzyme in the active site
malfunction
-
mutation S298P leads to 97.7% reduced enzyme activity and proteasomal degradation of the mutant enzyme causing the mild clinical phenotype of Sanfilippo A syndrome or Mucopolysaccharidosis type IIIA, a fatal inherited lysosomal storage disease accompanied by progressive neurologic degeneration, overview. PPatients are objects for early sulfamidase replacement therapy or treatment with selective pharmacological chaperones. Treatments with several pharmacological chaperones, such as nojirimycin, deoxygalactonojirimycin, deoxymannojirimycin, N-butyldeoxynojirimycin, phenylbutyric acid, at various concentrations do not increase the sulfamidase activity in S298P mutant expressing cells
malfunction
-
deficient N-sulfoglucosamine sulfohydrolase enzyme activity causes mucopolysaccharidosis (MPS) type IIIA
malfunction
-
deficient N-sulfoglucosamine sulfohydrolase enzyme activity causes mucopolysaccharidosis (MPS) type IIIA
malfunction
mucopolysaccharidoses are a group of recessively inherited lysosomal storage disorders caused by a deficiency of enzymes involved in the metabolic breakdown of glycosaminoglycans. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase, more than 100 mutations in the SGSH gene are found to reduce or eliminate its enzymatic activity. The Sanfilippo syndrome signs of neurodegeneration are the initial symptoms and comprise of hyperactivity, developmental stagnation and psychomotor regression
malfunction
mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A) is a lysosomal storage disorder caused by a deficiency of the enzyme heparan-N-sulfatase (EC 3.10.1.1), leading to accumulation of the glycosaminoglycan, heparan sulfate, in the lysosomes
malfunction
mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A) is a neurodegenerative lysosomal storage disorder caused by the deficiency of sulphamidase enzyme (SGSH) leading to accumulation of heparan sulfate
malfunction
mucopolysaccharidosis Type IIIA (MPSIIIA, Sanfilippo A syndrome), is an inherited neurodegenerative disease caused by mutations in the lysosomal enzyme, N-sulfoglucosamine sulfohydrolase. Mutations in the SGSH enzyme, the only mammalian heparan N-sulfatase, cause accumulation of lysosomal inclusion bodies in brain cells comprising heparan sulfate glycosaminoglycans. Systemic administration of MPSIIIA mice with the cTfRMAb-SGSH (IgG-SGSH fusion protein, where the IgG domain is a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR)) fusion protein causes a 70% reduction in brain heparan sulfate, the pathologic glycosaminoglycan of the central nervous system in MPSIIIA
malfunction
Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA) is a lysosomal disorder wherein deficient heparan-N-sulfatase (HNS) activity results in the accumulation of heparan sulfate in the central nervous system and is associated with progressive neurodegeneration in early childhood
malfunction
-
deficient N-sulfoglucosamine sulfohydrolase enzyme activity causes mucopolysaccharidosis (MPS) type IIIA
-
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