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Information on EC 3.10.1.1 - N-sulfoglucosamine sulfohydrolase
for references in articles please use BRENDA:EC3.10.1.1
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EC Tree 3 Hydrolases
3.10 Acting on sulfur-nitrogen bonds
3.10.1 Acting on sulfur-nitrogen bonds (only sub-subclass identified to date)
3.10.1.1 N-sulfoglucosamine sulfohydrolase
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 3.10.1.1
- mucopolysaccharidosis
- lysosomal
-
sanfilippo
-
mps-iiia
- naglu
-
n-sulfate
-
sulfate-derived
- heparinum
- medicine
- oestrone
- hgsnat
- sumf1
-
iduronate
-
sulfatases
-
ubiquitin-positive
- drug development
- pharmacology
- diagnostics
showSynonyms
sulfamidase, sgsh, sulphamidase, sulphohydrolase, n-sulfoglucosamine sulfohydrolase, heparin sulfamidase, n-sulphoglucosamine, heparan-n-sulfatase, sulphamate sulphohydrolase, heparan-n-sulphatase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-desoxy-2-sulphamido-D-glucose sulphamidase
-
-
-
-
2-desoxy-D-glucoside-2-sulphamate sulphohydrolase
-
-
-
-
heparan-N-sulfatase
heparin sulfamidase
-
-
-
-
N-sulfoglucosamine sulfohydrolase
SGSH
sulfamidase
sulfoglucosamine sulfamidase
-
-
-
-
sulphamate sulphohydrolase
-
-
-
-
sulphamidase
sulphamidase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
N-sulfo-D-glucosamine + H2O = D-glucosamine + sulfate
-
-
-
-
N-sulfo-D-glucosamine + H2O = D-glucosamine + sulfate
catalytic reaction mechanism: the active-site formylglycine (FGly70), which is intrinsically reactive, undergoes hydration to form the resting state of the enzyme with a gem-diol group (step 1). Coordination of one of the hydroxyl groups of the gem-diol to a Ca2+ ion facilitates the development of a negative charge on the O atom as its proton is lost to a base. The negatively charged O atom nucleophilically attacks the sulfur centre of the N-linked sulfate group on the glucosamine substrate (step 2), resulting in a covalently bound enzyme-substrate complex with a pentavalent sulfur transition state. An acid (possibly His181) facilitates the cleavage of the S-N bond by protonating the bridging N atom to form an amine leaving group on the N-desulfated substrate, which diffuses away, leaving an O-sulfated enzyme (step 3). Finally, in a step that underlines the importance of the formylglycine residue, another base (His125) deprotonates the second hydroxyl group, resulting in a negatively charged O atom (step 4) that forms a double bond with the C atom as the C-O bond between it and the bridging O atom of the sulfate group breaks, eliminating the sulfate ion and regenerating the formylglycine residue (step 5)
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis
-
-
hydrolysis of an N-linked sulfate group from the non-reducing terminal glucosaminide residues of heparan sulfate
-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
heparan sulfate degradation, heparin degradation
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SYSTEMATIC NAME
IUBMB Comments
N-sulfo-D-glucosamine sulfohydrolase
-
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CAS REGISTRY NUMBER
COMMENTARY
37289-41-1
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-deoxy-2-sulfamido-D-glucose + H2O
2-deoxy-2-amino-D-glucose + sulfate
-
Substrates: -
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2-sulfamate-2-deoxy-1-alpha-(2-naphthyl)-glucopyranoside + H2O
2-amino-2-deoxy-1-alpha-(2-naphthyl)-glucopyranoside + sulfate
Substrates: -
Products: -
Products: -
?
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
N-sulfo-D-glucosamine + H2O
D-glucosamine + sulfate
-
Substrates: -
Products: -
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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
-
Substrates: -
Products: -
Products: -
?
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
Substrates: -
Products: -
Products: -
?
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
-
Substrates: -
Products: -
Products: -
?
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
-
Substrates: -
Products: -
Products: -
?
glucosamine 2,6-disulfate + H2O
D-glucosamine 6-sulfate + sulfate
-
Substrates: -
Products: -
Products: -
ir
glucosamine 2,6-disulfate + H2O
D-glucosamine 6-sulfate + sulfate
-
Substrates: no activity with purified enzyme
Products: -
Products: -
?
heparan sulfate + H2O
? + sulfate
-
Substrates: -
Products: -
Products: -
?
heparan sulfate + H2O
? + sulfate
-
Substrates: degradation of heparan sulfate
Products: -
Products: -
?
heparan sulfate + H2O
? + sulfate
-
Substrates: -
Products: -
Products: -
?
heparin + H2O
? + sulfate
-
Substrates: degradation products of
Products: -
Products: -
?
additional information
?
-
-
Substrates: overview: effect of aglycone structure
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
heparan sulfate + H2O
? + sulfate
-
Substrates: -
Products: -
Products: -
?
heparan sulfate + H2O
? + sulfate
-
Substrates: degradation of heparan sulfate
Products: -
Products: -
?
heparan sulfate + H2O
? + sulfate
-
Substrates: -
Products: -
Products: -
?
heparin + H2O
? + sulfate
-
Substrates: degradation products of
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SUMF1
-
i.e. sulfatase modifying factor 1, exhibits an enhancing effect on sulfatase activity when coexpressed with sulfatases, overview
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0107
tetrasaccharides
-
substrates deriving from heparan sulfate, unamplified recombinant enzyme
-
0.01225
tetrasaccharides
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substrates deriving from heparan sulfate, gene-amplified recombinant enzyme
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.7
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 6
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
an adult Sanfilippo type A patient with homozygous mutation R206P in the sulfamidase gene shows a mild clinical phenotype characterized essentially by a moderate nonevolving metal retardation, polymorphism R456H is also found
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
sulphamidase activity is undetectable in liver, kidney, brain, and spleen from untreated mucopolysaccharidosis type IIIA mice, whereas levels of sulphamidase activity in the liver, kidney, and spleen of mucopolysaccharidosis type IIIA mice treated with the sulphamidase vector averaged 68%, 5%, and 186% of normal activity, respectively
brenda
-
newborn and adult mucopolysaccharidosis type IIIA brain cells have approximately 5.7% of the sulfamidase activity present in primary neural cells cultured from unaffected newborn and adult mice
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
malfunction
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
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
-
deficient N-sulfoglucosamine sulfohydrolase enzyme activity causes mucopolysaccharidosis (MPS) type IIIA
malfunction
-
deficient N-sulfoglucosamine sulfohydrolase enzyme activity causes mucopolysaccharidosis (MPS) type IIIA
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 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
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
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
-
deficient N-sulfoglucosamine sulfohydrolase enzyme activity causes mucopolysaccharidosis (MPS) type IIIA
-
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SPHM_HUMAN
502
0
56695
Swiss-Prot
other Location (Reliability: 3)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
56000
63000
56000
-
x * 56000, mature recombinant enzyme, SDS-PAGE, x * 63000, unprocessed recombinant enzyme, SDS-PAGE
63000
-
x * 56000, mature recombinant enzyme, SDS-PAGE, x * 63000, unprocessed recombinant enzyme, SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
recombinant enzyme, crystal structure analysis. Two SGSH monomers associate noncovalently to form a butterfly-shaped homodimer burying approximately 10.3% of the accessible surface area of each subunit
additional information
the monomeric enzyme subunit comprises of two domains, each centred on a beta-sheet: a large N-terminal domain (domain 1) and a smaller C-terminal domain (domain 2), as is typical for the sulfatase fold. There are 14 beta-strands, 13 alpha-helices and six 310-helices (T1-T6) in total
?
-
x * 56000, mature recombinant enzyme, SDS-PAGE, x * 63000, unprocessed recombinant enzyme, SDS-PAGE
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
Asn41, Asn151, Asn264 and Asn413 are four of the five N-glycosylation sites
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant C-terminally His6-tagged, glycosylated full-length enzyme, small unit and large unit crystal forms, X-ray diffraction structure determination and analysis at 2.0-2.4 A resolution, molecular replacement. The enzyme appears to exist as a homodimer in both crystal forms
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G191R
mutation identified in children with mucopolysaccharidosis type IIIA in Germany. Recombinant mutant enzyme shows no activity
L163P
mutation identified in children with mucopolysaccharidosis type IIIA in Germany. Recombinant mutant enzyme shows no activity
R206P
-
an adult Sanfilippo type A patient with homozygous mutation R206P in the sulfamidase gene shows a mild clinical phenotype characterized essentially by a moderate nonevolving metal retardation, polymorphism R456H is also found
R233X
mutation identified in children with mucopolysaccharidosis type IIIA in Germany. Recombinant mutant enzyme shows no activity
R433W
mutation identified in children with mucopolysaccharidosis type IIIA in Germany. Recombinant mutant enzyme shows no activity
R74C
mutation identified in children with mucopolysaccharidosis type IIIA in Germany. Recombinant mutant enzyme shows no activity
S106R
mutation identified in children with mucopolysaccharidosis type IIIA in Germany. Recombinant mutant enzyme shows 3.3% of wild-type activity
S298P
Y403del
mutation identified in children with mucopolysaccharidosis type IIIA in Germany. Recombinant mutant enzyme shows no activity
additional information
S298P
-
site-directed mutagenesis, the mutant shows a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA, phenotype, overview
S298P
-
naturally occuring mutation involved in the Sanfilippo A syndrome, mutations Arg61SfsX69, Ser66Trp, Arg74Cys, Arg245His, Gly251Ala, Tyr403del, c.949þ1G>C, are accompanying it on the other allele
additional information
-
construction of a mouse line carrying a null mutation in the Sumf1 gene, sulfatase activities are completely absent in Sumf1-/- mice, which display frequent early mortality, congenital growth retardation, skeletal abnormalities, and neurological defects, tissues show progressive cell vacuolization, significant lysosomal storage of glycosaminoglycans and a generalized inflammatory process characterized by a massive presence of highly vacuolated macrophages, phenotype, overview
additional information
-
co-delivery of SUMF1 and SGSH, via an AAV2/5-CMV-SGSH-IRES-SUMF1 vector, results in a synergistic increase in SGSH activity, both in primary neural cells and in murine brain, in mucopolysaccharidosis type IIIA, effects on phenotype, overview
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 7.4
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4, sodium acetate, pH 5.0, 30% glycerol, 25 mM NaCl, 0.1 mM DTT, 0.3 mg/ml BSA, 3 month
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally His6-tagged full-length enzyme from HEK-293 cells by nickel affinity croomatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and anaylsis, genotyping of patients with mucopolysaccharidosis type IIIA, overview
-
expression of GFP-tagged enzyme in mouse brain via injection into brain of MPS-IIIA mice, expression anaylsis, co-expression with sulfatase modifying factor 1, overview
-
gene SGSH, DNA and amino acid sequence determination and analysis, expression of mutant S298P sulfamidase in BHK cells, rapid degradation is responsible for the low steady state level of the mutant protein. Only small amounts of the S298P sulfamidase are transported to the lysosomes after processing and secretion, most of the mutant sulfamidase exits the endoplasmic reticulum for proteasomal degradation
-
heterologous expression, using a baculovirus system, of the cDNAs corresponding to eight out of 14 mutant alleles present in the patient group of 26 unrelated Spanish patients with mucopolysaccharidosis IIIA. Expression of the following alleles: p.S66W, p.R74H, p.Q85R, p.R206P, p.L386R, p.R433W, p.R433Q, and c.1079delC. Expression of wild-type and mutant sulfamidases in Sf9 insect cells
-
isolation of a CHO-K1 cell line expressing levels of recombinant sulfamidase at levels up to 4 mg/l of culture medium
-
recombinant expression of C-terminally His6-tagged full-length enzyme in HEK-293 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme activity is significantly reduced in mucopolysaccharidosis type IIIA patients
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
-
a fluorimetric SGSH activity assay is commonly used to examine cells of mucopolysaccharidosis type IIIA patients for N-sulfoglucosamine sulfohydrolase activity, modification of the method for brain homogenates and definition of the parameters for assay linearity, overview
drug development
the enzyme is a target for the development of structure-based drug design for the devastating neurodegenerative disorder mucopolysaccharidosis type IIIA or Sanfilippo A syndrome
medicine
pharmacology
-
early treatment of CNS lesions by adeno-associated virus-mediated intraventricular injection of both SGSH and SUMF1 genes may represent a feasible therapy for MPS-IIIA
medicine
-
intracerebral injection of recombinant human sulfamidase delays neuropathology in murine MPS-IIIA. Treatment reduces vacuolation and gliosis and delays the onset of ubiquitin-positive neurodegenerative changes in widespread areas of mucopolysaccharidosis type IIA brain, assessed at 24 weeks of age
medicine
-
the relative quantification of hexosamine-N-sulfate[alpha-1,4]hexuronic acid should prove to be a useful indicator of the effectiveness of enzyme replacement therapy within the mucopolysaccharidosis type IIIA mouse central nervous system
medicine
-
enzyme-replacement therapy from birth delays the development of behavior and learning problems in mucopolysaccharidosis type IIIA mice. Recombinant human sulfamidase administered to mucopolysaccharidosis type IIIA mice
medicine
-
recombinant murine sulfamidase is able to correct the storage phenotype of mucopolysaccharidosis type IIIA fibroblasts after endocytosis via the mannose-6-phosphate receptor
medicine
-
the enzyme might be an immediately applicable method for in vivo to treatment of lysosomal disorders like mucopolysaccharidosis type IIIA and similar lysosomal diseases in the central nervous system
medicine
-
mucopolysaccharidosis type IIIA is caused by a deficiency in sulphamidase
medicine
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. Primary stored heparan sulfate and other glycosaminoglycans possibly accumulated through a secondary storage in brain, liver, kidney and lung of MPS IIIA mouse model is quantitatively and structurally characterized. The analysis is also performed in MPS IIIA mice upon the intravenous treatment with an engineered human sulphamidase (chimeric hSGSH) capable to increase its secretion from the liver and to cross the bloodbrain barrier. MPS IIIA animals show a huge accumulation of heparan sulfate, from about 15 up to about 24times higher than wild type and also of hyaluronic acid (from 2.5 up to about 5.0times more) and chondroitin sulfate/dermatan sulfate (from about 2 up to about 5times more) in all studied organs. A significant increase in the overall heparan sulfate charge density is observed and in particular of 2-O-sulfation in MPS IIIA mice organs. 8 months after a systemic treatment with an engineered SGSH, the enzyme is highly efficient in the reduction of all accumulated glycosaminoglycans in liver, brain and lung up to values of wild type mice. Even if reduced, glycosaminoglycans levels still remain significantly elevated in kidney. The data obtained by analysis of glycosaminoglycans in the different organs of affected and treated animals with chimeric human sulphamidase enzyme may have implications for the evaluation of an effective therapeutic option of MPS IIIA and for the reduction of related neuropathology
medicine
administration of recombinant human heparan-N-sulfatase via intrathecal drug delivery device appears generally safe and well tolerated in patients with mucopolysaccharidosis IIIA. Treatment results in consistent declines in heparan sulfate in cerebrospinal fluid, suggesting in vivo activity in the relevant anatomical compartment
medicine
intrathecal administration of recombinant human heparan-N-sulfatase reduces heparan sulfate and glycosaminoglycan levels in treated patients
medicine
-
the enzyme can be used for treatment in patients with Sanfilippo syndrome type A (mucopolysaccharidosis IIIA)
medicine
the enzyme activity is a biomarker for mucopolysaccharidosis type IIIA therapy
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Homo sapiens
brenda
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