Information on EC 3.2.1.76 - L-iduronidase

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The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY
3.2.1.76
-
RECOMMENDED NAME
GeneOntology No.
L-iduronidase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydrolysis of unsulfated alpha-L-iduronosidic linkages in dermatan sulfate
show the reaction diagram
-
-
-
-
hydrolysis of unsulfated alpha-L-iduronosidic linkages in dermatan sulfate
show the reaction diagram
active site structure, active site residues, overview
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Glycosaminoglycan degradation
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
glycosaminoglycan alpha-L-iduronohydrolase
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Aldurazyme
-
commercial preparation
alpha-iduronidase
-
-
alpha-L-iduronidase
-
-
-
-
alpha-L-iduronidase
-
-
alpha-L-iduronidase
-
alpha-L-iduronidase
-
-
alpha-L-iduronidase
Mus musculus C57BL/6
-
-
-
alpha-L-iduronidase A
-
-
hIDUA
-
-
IDUA
Mus musculus C57BL/6
-
-
-
iduronidase
-
-
additional information
-
the enzyme belongs to the CAZY 39 structural family
CAS REGISTRY NUMBER
COMMENTARY
9073-56-7
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
the enzyme belongs to the glycosyl hydrolase family 39, GH39
evolution
-
the enzyme belongs to glycoside hydrolase family 39, GH39
malfunction
-
mutations in the IDUA gene cause mucopolysaccharidosis type I, MPS I, a progressive multisystem disorder with features ranging over a continuum from mild to severe which is inherited in an autosomal recessive manner
malfunction
-
mutations in the IDUA gene cause mucopolysaccharidosis type I, MPS I, a progressive multisystem disorder
malfunction
-
enzyme deficiency causes mucopolysaccharidosis I, MCS I
malfunction
-
mucopolysaccharidosis type I arises from a deficiency in the alpha-L-iduronidase enzyme
malfunction
-
mucopolysaccharidosis type I is caused by a deficiency in lysosomal alpha-L-iduronidase activity
malfunction
-
enzyme deficiency causes mucopolysaccharidosis type I, patients with MPS I developmental retardation, gross facial features, an enlarged and deformed skull, a small stature, corneal opacities, hepatosplenomegaly, valvular heart defects, thick skin, joint contractures and hernias
malfunction
-
mucopolysaccharidosis I is an autosomal recessive lysosomal storage disease due to deficient alpha-L-iduronidase activity. It results in the accumulation of the glycosaminoglycans heparan and dermatan sulfate and leads to several clinical manifestations
malfunction
-
deficiency of the enzyme leads to progressive accumulation of glycosaminoglycans, dermatan and heparan sulfate, in all organs and tissues, mucopolysccharidosis I is a lysosomal storage disorder that results from deficiency in the lysosomal enzyme alpha-L-iduronidase. Infusions of intravenous enzyme improves hepatosplenomegaly, pulmonary function, ambulation, jointmobility, cardiac function, and cognitive and neuroradiological progress
malfunction
-
mucopolysaccharidosis type I, MPS I, is an autosomal recessively inherited lysosomal storage disorder caused by the lack of alpha-L-iduronidase which leads to accumulation of glycosaminoglycans in the lysosome, genotyping of cell lines with residual enzyme activity, overview
physiological function
-
the enzyme is involved in the degradation of the glycosaminoglycans dermatan sulfate and heparan sulfate
malfunction
-
enzyme dysfunction causes accumulation of dermatan/heparan sulfate leading to mucopolysaccharidosis type I. The defect of the enzyme leads to excess storage of dermatan/heparan sulfate and causes a systemic disorder, MPS I, involving progressive mental retardation, gross facial features, an enlarged and deformed skull, a small stature, corneal opacities, hepatosplenomegaly, valvular heart defects, thick skin, joint contractures, and hernias
additional information
-
the enzyme uses its own N-glycan as a substrate binding and catalytic module. The mannose residue of the N-glycan attached to N372 constitutes a part of the substrate-binding pocket and interacts directly with a substrate. The kinetics of native and deglycosylated hIDUA suggest that the N-glycan is also involved in catalytic processes. Concanavalin A pull-down assay shows that PNGase F-resistant N-glycans are essential for the enzyme activity. Enzyme and substrate binding site structures and enzyme-substrate interaction analysis, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4-methylcoumarin-7-yl-alpha-L-iduronic acid + H2O
4-methylcoumarin + alpha-L-iduronic acid
show the reaction diagram
-
design and development of an improved and less expensive synthesis method for the fluorogenic substrate, overview. The method is based on the double ketal fixation of the 1,2 and 3,5-hydroxy groups of D-glucose to form a cis-anti-cis-fused tricyclic D-glucofuranosyl derivative, which could undergo elimination to form a 5-exo-double bond followed by electrophilic addition, a Mitsunobu-type glycosylation reaction is used for the coupling of the hemiacetal with the acceptor
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
?
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
?
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
?
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
?
show the reaction diagram
-
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferol + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferol + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferol + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferol + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + H2O
4-methylumbelliferol + alpha-L-iduronic acid
show the reaction diagram
Mus musculus C57BL/6
-
-
-
?
4-methylumbelliferyl-alpha-L-iduronide + methanol
?
show the reaction diagram
-
methanolysis
-
-
?
4-methylumbelliferyl-alpha-L-iduronoside + H2O
4-methylumbelliferone + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-nitrophenyl-alpha-L-idopyranosiduronate + H2O
4-nitrophenol + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
4-nitrophenyl-alpha-L-iduronide + H2O
4-nitrophenol + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
5-fluoro-alpha-L-idopyranosyluronic acid fluoride + H2O
fluoride + ?
show the reaction diagram
-
-
-
?
alpha-L-iduronisyl-(alpha-1,3)-anhydrotalitol 4-sulfate + H2O
?
show the reaction diagram
-
-
-
-
-
alpha-L-iduronisyl-(alpha-1,3)-anhydrotalitol 4-sulfate + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-L-iduronisyl-(alpha-1,4)-anhydrotalitol 4-sulfate + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol 6-sulfate + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-L-iduronosyl(1-4)anhydromannitol-6-sulfate + H2O
?
show the reaction diagram
-
-
-
?
alpha-L-iduronysyl-(alpha-1,4)2,5-anhydro-D-mannitol-6-sulfate + H2O
2,5-anhydro-D-mannitol 6-sulfate + alpha-L-iduronic acid
show the reaction diagram
-
-
-
?
anhydromannitol iduronide + H2O
?
show the reaction diagram
-
-
-
-
?
dermatan sulfate + H2O
? + alpha-iduronic acid
show the reaction diagram
-
-
-
?
gheparan sulfate + H2O
? + alpha-iduronic acid
show the reaction diagram
-
-
-
?
glycosaminoglycan + H2O
? + alpha-iduronic acid
show the reaction diagram
-
-
-
?
phenyl alpha-L-iduronide + H2O
?
show the reaction diagram
-
-
-
-
-
phenyl alpha-L-iduronide + H2O
?
show the reaction diagram
-
-
-
-
?
phenyl alpha-L-iduronide + H2O
?
show the reaction diagram
-
-
-
-
?
IdoA-GlcNAc6S-IdoA2S-anM6S + H2O
?
show the reaction diagram
-
O-(alpha-L-iduronic acid)-(1,4)-D-O-(alpha-N-acetylglucosamine 6-sulphate)-L-O-(alpha-iduronic acid 2-sulphate)-O-D-2,5-anhydro-D-mannitol 6-sulphate
-
-
?
additional information
?
-
-
cleaves alpha-L-iduronic acid from the nonreducing ends of dermatan sulfate, heparin, and heparan sulfate, deficiency in alpha-L-iduronidase causes mucopolysaccharidosis type I
-
-
-
additional information
?
-
-
involved in the degradation of dermatan sulfate and heparan sulfate
-
-
-
additional information
?
-
-
involved in the degradation of dermatan sulfate and heparan sulfate, deficiency in alpha-L-iduronidase causes mucopolysaccharidosis type I
-
-
-
additional information
?
-
-
enzyme deficiency causes mucopolysaccharidosis type I, MPSI
-
-
-
additional information
?
-
-
enzyme deficiency causes the lysosomal storage disorder mucopolysaccharidosis type I, MPSI
-
-
-
additional information
?
-
the enzyme is involved in mucopolysaccharidosis type I
-
-
-
additional information
?
-
-
the enzyme is involved in the sequential degradation of heparan sufate and dermatan sulfate, enzyme deficiency results in the accumulation and urinary secretion of partially degraded glycosaminoglycans and causes the lysosomal storage disorder mucopolysaccharidosis type I, MPSI
-
-
-
additional information
?
-
-
substrate specificity of recombinant enzyme with and without a C-terminal ER-retention signal from seeds of Brassica napus and Nicotiana tabacum, overview
-
-
-
additional information
?
-
-
the enzyme cleaves terminal alpha-iduronic acid residues from glycosaminoglycan, heparan sulfate and dermatan sulfate
-
-
-
additional information
?
-
-
the enzyme hydrolyses the glycosidic bond between the terminal L-iduronic acid and the second sugar of N-acetylgalactosamine-4-sulfate/N-sulfo-D-glucosamine-6-sulfate, which are the major components of dermatan/heparan sulfate
-
-
-
additional information
?
-
-
the enzyme hydrolyzes terminal iduronic acid residues on glycosaminoglycans
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
alpha-L-iduronisyl-(alpha-1,3)-anhydrotalitol 4-sulfate + H2O
?
show the reaction diagram
-
-
-
-
-
alpha-L-iduronisyl-(alpha-1,4)-anhydrotalitol 4-sulfate + H2O
?
show the reaction diagram
-
-
-
-
-
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol + H2O
?
show the reaction diagram
-
-
-
-
-
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol 6-sulfate + H2O
?
show the reaction diagram
-
-
-
-
-
anhydromannitol iduronide + H2O
?
show the reaction diagram
-
-
-
-
-
dermatan sulfate + H2O
? + alpha-iduronic acid
show the reaction diagram
-
-
-
?
gheparan sulfate + H2O
? + alpha-iduronic acid
show the reaction diagram
-
-
-
?
glycosaminoglycan + H2O
? + alpha-iduronic acid
show the reaction diagram
-
-
-
?
additional information
?
-
-
cleaves alpha-L-iduronic acid from the nonreducing ends of dermatan sulfate, heparin, and heparan sulfate, deficiency in alpha-L-iduronidase causes mucopolysaccharidosis type I
-
-
-
additional information
?
-
-
involved in the degradation of dermatan sulfate and heparan sulfate
-
-
-
additional information
?
-
-
involved in the degradation of dermatan sulfate and heparan sulfate, deficiency in alpha-L-iduronidase causes mucopolysaccharidosis type I
-
-
-
additional information
?
-
-
enzyme deficiency causes mucopolysaccharidosis type I, MPSI
-
-
-
additional information
?
-
-
enzyme deficiency causes the lysosomal storage disorder mucopolysaccharidosis type I, MPSI
-
-
-
additional information
?
-
P35475
the enzyme is involved in mucopolysaccharidosis type I
-
-
-
additional information
?
-
-
the enzyme is involved in the sequential degradation of heparan sufate and dermatan sulfate, enzyme deficiency results in the accumulation and urinary secretion of partially degraded glycosaminoglycans and causes the lysosomal storage disorder mucopolysaccharidosis type I, MPSI
-
-
-
additional information
?
-
-
the enzyme cleaves terminal alpha-iduronic acid residues from glycosaminoglycan, heparan sulfate and dermatan sulfate
-
-
-
additional information
?
-
-
the enzyme hydrolyses the glycosidic bond between the terminal L-iduronic acid and the second sugar of N-acetylgalactosamine-4-sulfate/N-sulfo-D-glucosamine-6-sulfate, which are the major components of dermatan/heparan sulfate
-
-
-
additional information
?
-
-
the enzyme hydrolyzes terminal iduronic acid residues on glycosaminoglycans
-
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5R,6R,7S,8S)-5,6,7,8-tetrahydro-6,7,8-trihydroxytetrazolo[1,2-a]pyridine-5-carboxylate
-
-
(5R,6S,7S,8S)-5,6,7,8-tetrahydro-6,7,8-trihydroxytetrazolo[1,2-a]pyridine-5-carboxylate
-
-
(5S,6R,7S,8S)-5,6,7,8-tetrahydro-6,7,8-trihydroxytetrazolo[1,2-a]pyridine-5-carboxylate
-
-
2(S)-Carboxy-3(R),4(R),5(S)-trihydroxypiperidine
-
-
2,5-anhydro-D-mannitol
-
-
2,5-anhydro-D-mannitol 6-sulfate
-
-
2-fluoro-alpha-L-idopyranosyluronic acid fluoride
-
reversible, competitive with 4-nitrophenyl-alpha-L-idopyranosiduronate, activity drops down immediately after inhibitor is added
5-fluoro-alpha-L-idopyranosyluronic acid fluoride
-
reversible, competitive with 4-methylumbelliferyl-alpha-L-iduronide, activity drops down immediately after inhibitor is added
6-sodium-5-amino-5-deoxy-L-idarate-1,5-lactam
-
-
alpha-L-idosyl-(alpha-1,4)2,5-anhydro-D-mannitol 6-sulfate
-
-
-
Cu2+
-
-
CuCl2
-
-
CuCl2
-
strong noncompetitive inhibitor for enzyme from healthy individuals and mucopolysaccharidosis type I patients
D-saccharolactone
-
-
EDTA
-
competitive, equal inhibition of enzyme from healthy individuals and mucopolysaccharidosis type I patients
NaCl
-
-
NaCl
-
healthy individuals and 40% of heterocygotic mucopolysaccharidosis type I patients, activating for 60% of heterocygotic mucopolysaccharidosis type I patients
p-chloromercuribenzoate
-
-
SO42-
-
-
[(2S,3R,4R)-3,4-dihydroxy-5-oxotetrahydrofuran-2-yl](hydroxy)acetic acid
-
competitive inhibitor
Fe3+
-
-
additional information
-
not inhibited by 6-sodium 5-amino-5-deoxy-D-glucarate-1,5-lactam, 6-sodium 5-amino-5-deoxy-D-galactarate-1,5-lactam, 6-sodium 5-amino-5-deoxy-L-altrarate-1,5-lactam, and 4-amino-4,5-dideoxy-L-arabinaro-1,4-lactam
-
additional information
-
uptake of laronidase by F17 and F592 cells is strongly inhibited in the presence of 5.0 mmol/l mannose 6-phosphate in the culture medium. Uptake of the enzyme by MC3T3-E1 cells is strongly inhibited by the addition of 5.0 mmol/l M6P to the culture medium, but moderately inhibited by the addition of 5.0 mmol/l Man, as in the case of F665 cells
-
additional information
-
deglycosylation of the enzyme with endoglycosidase H, but not peptide-N-glycosidase F, reduces the enzyme's activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
-
dithiothreitol
-
-
glutathione
-
-
additional information
the synthesis of the CnABI3 (ABscisic acid Insensitive3) protein is able to transactivate the IDUA gene expression driven by the arcelin promoter, particularly in the presence of 0.15-0.2 mM (S)-(+)-abscisic acid
-
additional information
-
intracellular IDUA activity increases dose-dependently in both MC3T3-E1 and F665 cells. When laronidase is added to the medium at a low concentration (0.10 mg/ml) there is no difference in the uptake between them. Increase in the enzyme activity is always lower in MC3T3-E1 cells than in F665 ones when laronidase is added to the medium at the concentration of 1.0m g/ml or more, thus uptake of laronidase is lower in MC3T3-E1 cells than in F665 cells
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.031
4-Methylumbelliferyl alpha-L-iduronide
-
pH 4.2, 32C, recombinant wild-type enzyme
0.3
4-Methylumbelliferyl alpha-L-iduronide
-
pH 5.8, 37C, recombinant enzyme
0.015
4-methylumbelliferyl-alpha-L-iduronide
-
pH 4.5, 37C
0.04
4-methylumbelliferyl-alpha-L-iduronide
-
pH 4.8
0.07
4-methylumbelliferyl-alpha-L-iduronide
-
-
0.09
4-methylumbelliferyl-alpha-L-iduronide
-
-
0.1
4-methylumbelliferyl-alpha-L-iduronide
-
pH 2.8
0.18
4-methylumbelliferyl-alpha-L-iduronide
-
-
0.21
4-methylumbelliferyl-alpha-L-iduronide
-
pH 2.8, 37C, enzyme from healthy individuals in the presence of 10 mM CuCl2l
0.22
4-methylumbelliferyl-alpha-L-iduronide
-
pH 2.8, 37C, enzyme from healthy individuals
0.38
4-methylumbelliferyl-alpha-L-iduronide
-
37C, enzyme from mucopolysaccharidosis patients group II
0.45
4-methylumbelliferyl-alpha-L-iduronide
-
-
0.48
4-methylumbelliferyl-alpha-L-iduronide
-
pH 2.8, 37C, enzyme from healthy individuals in the presence of 20 mM EDTA
0.49
4-methylumbelliferyl-alpha-L-iduronide
-
37C, enzyme from mucopolysaccharidosis patients group I
0.6
4-methylumbelliferyl-alpha-L-iduronide
-
37C, enzyme from healthy individuals
0.81
4-methylumbelliferyl-alpha-L-iduronide
-
pH 2.8, 37C, enzyme from healthy individuals in the presence of 0.1 M NaCl
0.82
4-methylumbelliferyl-alpha-L-iduronide
-
-
1.92
4-methylumbelliferyl-alpha-L-iduronide
-
-
0.53
4-nitrophenyl-alpha-L-idopyranosiduronate
-
pH 4.5, 37C
0.08
alpha-L-iduronisyl-(alpha-1,3)-anhydrotalitol 4-sulfate
-
-
-
0.016
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol
-
pH 4.8
-
0.02
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol
-
pH 3
-
0.14
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol
-
-
-
0.01
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol 6-sulfate
-
pH 4.8
-
0.12
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol 6-sulfate
-
-
-
0.002
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol 6-sulfte
-
pH 2.7
-
9
anhydromannitol iduronide
-
-
-
0.001
IdoA-GlcNAc6S-IdoA2S-anM6S
-
pH 3.3
-
0.003
IdoA-GlcNAc6S-IdoA2S-anM6S
-
pH 4.8
-
0.001
IdoA-GlcNH6S-IdoA2S-anM6S
-
pH 3
-
0.001
IdoA-GlcNS6S-IdoA2S-anM6S
-
pH 3.6
-
0.2
phenyl alpha-L-iduronide
-
-
0.31
phenyl alpha-L-iduronide
-
L-iduronidase II
0.45
phenyl alpha-L-iduronide
-
L-iduronidase I
1.5
phenyl alpha-L-iduronide
-
-
0.002
IdoA-GlcNS6S-IdoA2S-anM6S
-
pH 4.8
-
additional information
additional information
-
kinetics of wild-type and mutant enzymes, overview
-
additional information
additional information
-
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.83
5-fluoro-alpha-L-idopyranosyluronic acid fluoride
Homo sapiens
-
pH 4.5, 37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5
(5R,6R,7S,8S)-5,6,7,8-tetrahydro-6,7,8-trihydroxytetrazolo[1,2-a]pyridine-5-carboxylate
-
Ki above 5 mM, at pH 4.5 and 37C
5
(5R,6S,7S,8S)-5,6,7,8-tetrahydro-6,7,8-trihydroxytetrazolo[1,2-a]pyridine-5-carboxylate
-
Ki above 5 mM, at pH 4.5 and 37C
1.3
(5S,6R,7S,8S)-5,6,7,8-tetrahydro-6,7,8-trihydroxytetrazolo[1,2-a]pyridine-5-carboxylate
-
at pH 4.5 and 37C
0.0046
2-fluoro-alpha-L-idopyranosyluronic acid fluoride
-
pH 4.5, 37C
0.0012
5-fluoro-alpha-L-idopyranosyluronic acid fluoride
-
pH 4.5, 37C
0.094
6-sodium-5-amino-5-deoxy-L-idarate-1,5-lactam
-
at pH 4.5 and 37C
1831
NaCl
-
pH 2.8, 37C, enzyme from healthy individuals
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0000014 - 0.000027
-
mucopolysaccharidosis type I mutant enzymes, immunocapture-enriched from skin fibroblast
0.000005 - 0.00011
-
activity levels from the same specimens of heterozygous mice vary greatly with different substrate concentrations of 4-methylumbelliferyl-alpha-L-iduronide, comparison of activities in livers at 15 different concentrations, overview. pH and temperature not specified in the publication
0.00003 - 0.000093
-
wild-type enzyme, immunocapture-enriched from skin fibroblast
0.0006
-
recombinant wild-type enzyme, CHO cells
0.0029
-
recombinant enzyme, using 4-methylumbelliferyl-alpha-L-iduronide as a substrate
0.0033 - 0.0053
-
wild-type cell lines, pH not specified in the publication, 37C
0.018
-
native enzyme, using 4-methylumbelliferyl-alpha-L-iduronide as a substrate
0.03
-
recombinant enzyme, using 4-methylumbelliferyl-alpha-L-iduronide as a substrate
0.3
-
recombinant mutant G265R, CHO cells
0.6
-
recombinant wild-type enzyme, CHO cells
1.5
-
recombinant mutant A79V, CHO cells
2.08
-
-
2.1
-
recombinant mutant L238Q, CHO cells
2.9
-
recombinant mutant F602I, CHO cells
4.8
-
recombinant mutant H82Q, CHO cells
6.7
-
recombinant mutant S423R, CHO cells
16
-
phenyl alpha-L-iduronide as substrate
32
-
purified recombinant enzyme expressed from Brassica napus seeds
34.9
-
-
39.7
-
purified recombinant enzyme expressed from Nicotiana tabacum seeds
87.5
-
soluble form
109
-
membrane associated form
270
-
anhydromannitol iduronide as substrate
5000 - 10000
-
-
126000
-
-
additional information
-
specific activity in healthy individuals was found to be higher than specific activity in mucopolysaccharidosis patients group I but similar with mucopolysaccharidosis patients group II
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3 - 3.5
-
both forms
3 - 3.5
-
-
3.4
-
assay at
4
-
phenyl alpha-L-iduronide as substrate
4.2
-
assay at
4.4
-
anhydromannitol iduronide as substrate
4.5
-
anhydromannitol as substrate
4.5
-
assay at
5.8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3.5 - 7.5
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21
-
assay at
22 - 37
-
assay at
32
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
low activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
purified recombinant enzyme
Manually annotated by BRENDA team
-
recombinant enzyme expressed in CHO cells
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
heterozygous mice
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
heterozygous mice
-
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
from healthy humans and mucopolysaccharidosis type I patients
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
with transfected CHO-K1 cells less than 10% of enzyme is found to be secreted into the medium
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60000
-
gel filtration
171555
60000
-
sedimentation equilibrium
171564
65000
-
gel filtration, form I and II from liver
171556
67000
-
gel filtration, L-iduronidase II
171554
68000
-
gel filtration, soluble form
171563
69000
-
Western blot analysis, mature component after incorporation into cells
696554
70000
-
gel filtration
171557
74000
-
wild type enzyme, SDS-PAGE, intracellulary processed to form fragments of 69000 Da and 65000 Da
655683
74000
-
SDS-PAGE
681942
76000
-
Western blot analysis, mature component after incorporation into cells
696554
79000
SDS-PAGE
682391
83000
-
Western blot analysis, before incorporation into cells
696554
85000
-
gel filtration, membrane associated form
171563
87000
-
gel filtration, L-iduronidase I
171554
480000
-
gel filtration and native PAGE
732391
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 77000, recombinant wild-tyype enzyme, extracellular secreted precursor enzyme form, SDS-PAGE, x * 74000, recombinant wild-type enzyme, intracellular precursor enzyme form, SDS-PAGE, x * 69000, recombinant wild-type enzyme, intracellular processed enzyme form 1, SDS-PAGE, x * 65000, recombinant wild-type enzyme, intracellular processed enzyme form 2, SDS-PAGE, x * 49000, recombinant wild-type enzyme, intracellular processed enzyme form 3, SDS-PAGE
?
-
x * 83000, recombinant wild-type enzyme, SDS-PAGE, x * 125000, recombinant RAP-fusion enzyme, SDS-PAGE
?
-
x * 78000, recombinant glycosylated enzyme, SDS-PAGE
?
-
x * 76600, recombinant glycosylated enzyme expressed from Brassica napus seeds, SDS-PAGE, x * 76700, recombinant glycosylated enzyme expressed from Nicotiana tabacum seeds, SDS-PAGE
?
-
x * 69908, sequence calculation
?
-
x * 69000
dimer
-
2 * 30000, SDS-PAGE
dimer
-
2 * 31000, SDS-PAGE
oligomer
-
x * 85000, SDS-PAGE
additional information
-
structure determination, PDB code 1Y24, using the crystal structure of the beta-xylosidase from Thermoanaerobacterium saccharolyticum, EC 3.2.1.37, structure modeling
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
contains glucosamine
glycoprotein
-
-
glycoprotein
-
oligomannose 7-bisphosphate is bound to the enzyme, with a much higher amount on the recombinant wild-type enzyme compared to the recombinant RAP fusion enzyme
glycoprotein
-
the enzyme is N-glycosylated. The carboxy-terminal endoplasmic reticulum-retention motif, SEKDEL, influences the N-linked glycosylation of the recombinant enzyme
glycoprotein
-
six potential N-glycosylation sites
glycoprotein
-
N-glycosylation, deglycoslyation b peptide N-glycosidase F from Flavobacterium meningosepticum and neuraminidase from Clostridium perfringens. The N-glycan pools consists of oligomannosidic glycans (mainly Man7, Man8, Man9 as well as Man9 + Glc), complex type glycans with up to three antennae. Sialylation as well as fucosylation are observed on almost all complex type glycans
glycoprotein
-
N-glycosylation at N110, N190, N336, N372, N415, and N451 in subunit A, and at N110, N190, N336, N372, N415, and N451 in subunit B, glycan structures, overview. The enzyme uses its own N-glycan as a substrate binding and catalytic module. The mannose residue of the N-glycan attached to N372 constitutes a part of the substrate-binding pocket and interacts directly with a substrate. The kinetics of native and deglycosylated hIDUA suggest that the N-glycan is also involved in catalytic processes. Deglycosylation of the enzyme with endoglycosidase H, but not peptide-N-glycosidase F, reduces the enzyme's activity. Concanavalin A pull-down assay shows that PNGase F-resistant N-glycans are essential for the enzyme activity
phosphoprotein
-
phosphorylations on S59 and S482, phosphatase treatment
proteolytic modification
-
-
proteolytic modification
-
84000Da to 69000Da
side-chain modification
-
N-linked oligosaccharides
side-chain modification
-
histidine methylation at H572
glycoprotein
-
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystallized from different solution using the hanging-drop crystallization method
-
purified recombinant enzyme, hanging drop vapour diffusion method, 4 mg/ml protein, mixing of 0.008 ml of both protein solution and reservoir solution, the latter containing 18% w/v PEG 3350, 0.18 M K/Na-tartrate, 3% w/v PEG MME 5000, 0.02 M ammonium sulfate, and 0.01 M MES-Na, pH 6.5, 25C, 2-3 days, X-ray diffraction structure determination and analysis at 2.3 A resolution, mercury-derivative crystals by single-wavelength anomalous dispersion data, Hg peak wavelength
-
structure analysis of enzyme-substrate complex, PDB IDs 3W81 and 3W82
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3
-
rapidly inactivated
171560
8
-
rapidly inactivated
171560
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50
-
enzyme from mucopolysaccharidosis patients is more stable than enzyme from healthy individuals
654383
55
-
both forms are stable over 30 min
171554
65
-
L-iduronidase II is more labile
171554
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the lysosomal (or tissue) half-life of recombinant human IDU appears to be approximately 6-7 days because a 3fold higher than normal enzyme level (300%) elevation is reduced to about 20% over a period of 28 days
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Methanol
-
quite stable towards molar concentrations of methanol
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, 0.03M sodium dimethylglutarate buffer, 10% glycerol, 0.5 M NaCl, pH 6 or 3.7, 18 months, 80% of activity retained
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
native and recombinant wild-type and mutant enzymes partially by immunoprecipitation
-
recombinant enzyme with and without a C-terminal ER-retention signal from seeds of Brassica napus and Nicotiana tabacum by lectinb affinity, immunoaffinity, and adsorption chromatography
-
recombinant wild-type enzyme and human receptor-associated protein RAP-fusion enzyme from LRP1-null CHO-K1 cells by heparin affinity and hydrophobic interaction chromatography, and gel fitration
-
the commercial preparation of recombinant enzyme expressed in CHO cells is further purified by gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Cos-1 cells
-
commercially available recombinant human iduronidase (Aldurazyme) produced in Chinese-hamster-ovary cells
-
expressed in Arabidopsis thaliana complex-glycan-deficient mutants
-
expressed in CHO cells
-
expressed in CHO-K1 cells
-
expressed in Mus musculus brain
-
expressed in Mus musculus liver, spleen, kidney, heart and lung
-
expressed in Nicotiana tabacum leaves
expressed in Rattus norvegicus primary neurons using lentivirus vectors
-
expression in CHO-K1 cells
-
expression in retroviral transduced fibroblasts
-
expression of IDUA with and without a C-terminal endoplasmic reticulum-retention sequence SEKDEL, in seeds of Brassica napus and Nicotiana tabacum under the control of regulatory 5'-, signal-peptide-encoding-, and 3'-sequences from the arcelin 5-I gene of Phaseolus vulgaris
-
expression of wild-type enzyme and enzyme in fusion with the human receptor-associated protein, RAP, in LRP1-null CHO-K1 cells
-
gene IDUA, screening and genotyping of nonsense, 4 missense, 1 deletion, and 2 splice site intron mutations in 10 MPS I patients, development and evaluation of a dHPLC screening method, overview
-
genotyping of different mucopolysaccharidosis type I patient cell lines, overview
-
human-mouse somatic cell hybrids
-
IDUA cloning in Escherichia coli strain BL21, and overexpression in transgenic Nicotiana tabacum BY-2 cells, establishing and evaluation of the expression system, overview. A plant signal peptide is essential for proper expression and secretion of the glycosylated recombinant hIDUA into the cultured media of transgenic BY-2 cells, transfection by Agrobacterium tumefaciens, strain LBA4404
-
IDUA gene, determination of mutant sequences from mucopolysaccharidosis type I enzymes, genotyping, expression of wild-type and mutant enzymes in CHO cells
-
incorporated via mannose 6-phosphate receptors into human fibroblasts from a patient with MPS I (F17) or a healthy subject (F592), into cultured mouse osteoblasts (MC3T3-E1) or cultured mouse fibroblasts (F665)
-
recombinant expression in baby hamster kidney cells
-
expression in Cos-1 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
following three repeat intrathecal administrations of 0.1 mg/kg recombinant human alpha-L-iduronidase or placebo on days 1, 4 or 5, and 9, two days after the final intrathecal injection, the mean tissue alpha-L-iduronidase activity in the brains of the two treated animals are approximately 3times higher than the activity found in normal cat brains and remains higher than untreated mucopolysaccharidosis type I brain at 1 month before returning to near-baseline levels after 2 months
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
134del12
-
homozygous genotype with only residual enzyme activity
A160D
-
severe mucopolysaccharidosis type I phenotype
A319V
-
attenuated mucopolysaccharidosis type I phenotype
A327P
-
severe mucopolysaccharidosis type I phenotype
A327P
-
naturally occuring mutation in the IDUA gene from an MPS I patient
A327P
-
A327P/A327P and A327P/unknown, naturally occuring homozygous and indefinite mutant genotypes with only residual enzyme activity at 37C; homozygous genotype with only residual enzyme activity
A327P/R383H
-
a genotype with only residual enzyme activity
A75T
-
severe mucopolysaccharidosis type I phenotype
A79V
-
naturally occurring mutation in the IDUA gene of a mucopolysaccharidosis type I patient, construction by site-directed mutagenesis for expression in CHO cells, the recombinant mutant shows about 2fold increased activity in CHO cell lysate and altered subcellular localization compared to the recombinant wild-type enzyme
A79V
-
intermediate mucopolysaccharidosis type I phenotype
A79V
-
the missense mutation is associated with mucopolysaccharidosis type I
C205Y
-
attenuated mucopolysaccharidosis type I phenotype
C577GfsX15
-
naturally occuring mutation in the IDUA gene from an MPS I patient
D203N
-
the missense mutation is associated with mucopolysaccharidosis type I
D315Y
-
severe mucopolysaccharidosis type I phenotype
D315Y
-
naturally occuring mutation in the IDUA gene from an MPS I patient
D349Y
-
severe mucopolysaccharidosis type I phenotype
E178K
-
intermediate mucopolysaccharidosis type I phenotype
E182A
-
catalytically inactive
E182K
-
mutation found in patients with mucopolysaccharidosis type I, catalytically inactive
E182K
-
severe mucopolysaccharidosis type I phenotype
E276K
-
E276K/E276K is a naturally occuring rare homozygous mutant genotype with only residual enzyme activity and thermal instability at 37C
E299A
-
catalytically inactive
E640Cfs
-
naturally occuring mutation in the IDUA gene from an MPS I patient
F602I
-
naturally occurring mutation in the IDUA gene of a mucopolysaccharidosis type I patient, construction by site-directed mutagenesis for expression in CHO cells, the recombinant mutant shows about 5fold increased activity in CHO cell lysate and altered subcellular localization compared to the recombinant wild-type enzyme
G208D
-
severe mucopolysaccharidosis type I phenotype
G208V
-
severe mucopolysaccharidosis type I phenotype
G265R
-
naturally occurring mutation in the IDUA gene of a mucopolysaccharidosis type I patient, construction by site-directed mutagenesis for expression in CHO cells, the recombinant mutant shows reduced activity in CHO cell lysate and altered subcellular localization compared to the recombinant wild-type enzyme
G51D
-
severe mucopolysaccharidosis type I phenotype
H240R
-
attenuated mucopolysaccharidosis type I phenotype
H82P
-
intermediate mucopolysaccharidosis type I phenotype
H82Q
-
naturally occurring mutation in the IDUA gene of a mucopolysaccharidosis type I patient, construction by site-directed mutagenesis for expression in CHO cells, the recombinant mutant shows 8fold increased activity in CHO cell lysate and altered subcellular localization compared to the recombinant wild-type enzyme
I270S
-
severe mucopolysaccharidosis type I phenotype
I270S/P533R/R268X
-
identification of naturally occurring mutation of a tunesian patient, homoallelic for P533R mutation, heteroallelic for missense mutation I270S and nonsense mutation R268X, and a deletion mutation in exon 13, the mutations are involved in development of the lysosomal storage disorder mucopolysaccharidosis type I, MPSI, the patient shows the Huler phenotype, overview
L218P
-
severe mucopolysaccharidosis type I phenotype
L218P
-
homozygous genotype with only residual enzyme activity
L238Q
-
naturally occurring mutation in the IDUA gene of a mucopolysaccharidosis type I patient, construction by site-directed mutagenesis for expression in CHO cells, the recombinant mutant shows about 3.5fold increased activity in CHO cell lysate and altered subcellular localization compared to the recombinant wild-type enzyme
L346R
-
intermediate mucopolysaccharidosis type I phenotype
L346R
-
the missense mutation is associated with mucopolysaccharidosis type I
L490P
-
intermediate mucopolysaccharidosis type I phenotype
N350I
-
attenuated mucopolysaccharidosis type I phenotype
P183R
-
severe mucopolysaccharidosis type I phenotype
P496L
-
intermediate mucopolysaccharidosis type I phenotype
P496R
-
severe mucopolysaccharidosis type I phenotype
P533R
-
identification of naturally occurring mutation of two tunesian patient, homoallelic for P533R mutation, the mutation is involved in development of the lysosomal storage disorder mucopolysaccharidosis type I, MPSI, the patient shows the Huler-Scheie phenotype, overview
P533R
-
homozygous genotype with only residual enzyme activity
Q380R
-
attenuated mucopolysaccharidosis type I phenotype
Q380R
-
naturally occuring mutation in the IDUA gene from an MPS I patient
Q584X
-
the missense mutation is associated with mucopolysaccharidosis type I
Q60X
-
the missense mutation is associated with mucopolysaccharidosis type I
Q70X
-
naturally occuring mutation in the IDUA gene from an MPS I patient
Q70X
-
homozygous genotype with only residual enzyme activity
Q70X/R383H
-
a genotype with only residual enzyme activity
R363C
-
naturally occurring mutation in the IDUA gene of a mucopolysaccharidosis type I patient, construction by site-directed mutagenesis for expression in CHO cells, inactive recombinant mutant
R363C
-
severe mucopolysaccharidosis type I phenotype
R363H
-
the missense mutation is associated with hepatosplenomegaly, joint stiffness, corneal clouding, and slightly mental delay in mucopolysaccharidosis type I patients and displays 2.3% of wild type activity
R383H
-
attenuated mucopolysaccharidosis type I phenotype
R383H
-
homozygous genotype with only residual enzyme activity
R489P
-
severe mucopolysaccharidosis type I phenotype
R492P
-
attenuated mucopolysaccharidosis type I phenotype
R619G
-
the missense mutation is associated with mucopolysaccharidosis type I
R621X/974ins12
-
a genotype with only residual enzyme activity
R628X
-
naturally occuring mutation in the IDUA gene from an MPS I patient
R89Q
-
protein level is lowered to 10% of normal control
R89Q
-
attenuated mucopolysaccharidosis type I phenotype
R98W
-
strongly reduced activity, protein level not effected
S260F
-
intermediate mucopolysaccharidosis type I phenotype
S423R
-
naturally occurring mutation in the IDUA gene of a mucopolysaccharidosis type I patient, construction by site-directed mutagenesis for expression in CHO cells, the recombinant mutant shows 11fold increased activity in CHO cell lysate and altered subcellular localization compared to the recombinant wild-type enzyme
T364M
-
intermediate mucopolysaccharidosis type I phenotype
T364M
-
the missense mutation is associated with mucopolysaccharidosis type I
T366P
-
severe mucopolysaccharidosis type I phenotype
T388R
-
severe mucopolysaccharidosis type I phenotype
V620F
-
naturally occuring mutation in the IDUA gene from an MPS I patient
W402X
-
naturally occuring mutation in the IDUA gene from an MPS I patient
W402X
-
the missense mutation is associated with mucopolysaccharidosis type I
W402X
-
homozygous genotype with only residual enzyme activity
W626X
-
naturally occuring mutation in the IDUA gene from an MPS I patient
Y167X
-
naturally occuring mutation in the IDUA gene from an MPS I patient
L490P
-
homozygous genotype with only residual enzyme activity
additional information
-
nonsense mutation of residue Q70 is involved in the disease mucopolysaccharidosis type I, MPSI, changes in hair morphology of MPSI patients treated with recombinant human enzyme in enzyme replacement therapy, overview
additional information
-
identification and molecular characterization of 14 different enzyme mutations and 13 different polymorphic changes present in 10 mucopolysaccharidosis type I patients undergoing enzyme replacement therapy
additional information
-
exploitation of alternative receptor systems that are independent of glycosylation but allow for efficient delivery to the lysosome, fusions of the human lysosomal enzyme with the receptor-associated protein, RAP, are efficiently endocytosed by lysosomal storage disorder patient fibroblasts, rat C6 glioma cells, mouse C2C12 myoblasts, and recombinant CHO cells expressing individual members of the low-density lipoprotein receptor family, uptake of the fusion exceeds that of phosphorylated enzyme in all cases, uptake is mediated by oligosaccharide receptors including the cation-independent mannose 6-phosphate receptor and the mannose receptor, and is specifically mediated by members of the low-density lipoprotein receptor protein family and is followed by delivery of the fusions to the lysosome, stability or recombinant fusion enzymes, overview
additional information
-
identification of naturally occurring mutations of residues Q70, W402, R268, Q400, Y343, W180 to premature stop codons, mutations are involved in development of the lysosomal storage disorder mucopolysaccharidosis type I, MPSI, natural stop codon read-through and clinical MPSI phenotype, overview
additional information
-
diverse missense mutations of the human enzyme's core, surface, and active site are correlated to the development of the lysosomal storage disorder mucopolysaccharidosis type I, MPSI, structural implications, detailed overview
additional information
-
over 100 disease-causing IDUA mutations identified in patients with mucopolysaccharidosis type I. Most common mutations that introduce premature stop codons are p.W402X and p.Q70X. Deficient IDUA activity results in the accumulation of dermatan and heparan sulfate in urine of affected individuals
additional information
-
gene IDUA, screening and genotyping of nonsense, 4 missense, 1 deletion, and 2 splice site intron mutations in 10 MPS I patients, development and evaluation of a dHPLC screening method, overview
additional information
-
construction of a protein mutant AGT-181, that is a genetically engineered fusion protein of human iduronidase and a chimeric monoclonal antibody against the human insulin receptor. The mutant AG-181 is administered to Maccaca mulatta, chronic AGT-181 dosing does not result in toxicity at any dose, and causes no changes in organ histology, no change in plasma or cerebrospinal fluid glucose, and no significant immune response. AGT-181 is rapidly removed from plasma, but shows iduronidase enzyme activity
additional information
-
mutations in the IDUA gene cause mucopolysaccharidosis type I, MPS I, a progressive multisystem disorder, phenotype with and without treatment with laronidase, overview
additional information
-
mutations in the IDUA gene cause mucopolysaccharidosis type I, MPS I, a progressive multisystem disorder, phenotypes, overview. Growth patterns in terms of body height, weight, head and chest circumference in patients with MPS I without treatment and after enzyme replacement therapy with alpha-L-iduronidase, overview
additional information
-
ability of recombinant baby hamster kidney cells transfected with human IDUA cDNA in correcting skin fibroblasts from mucopolysaccharidosis I patients in vitro, after encapsulation in alginate microcapsules, overview. The cells use the mannose-6-phosphate receptor to internalize the recombinant enzyme
Y343X
-
the missense mutation is associated with mucopolysaccharidosis type I
additional information
-
construction of knockout mice from C57BL/6 parents
additional information
Mus musculus C57BL/6
-
construction of knockout mice from C57BL/6 parents
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
intrathecal administration of recombinant human IDU, with potential dosing every 2-3 months, may provide benefit for the treatment of central nervous system disease in mucopolysaccharidosis type I patients
diagnostics
-
determining residual IDUA activity in fibroblasts of MPS I patients may be helpful to predict MPS I phenotype. Early recognition of the phenotype of MPS I patients is essential to timely initiate the most appropriate therapeutic strategy
drug development
-
mutant AGT-181 might be useful as a therapeutic approach to treatment of the brain in Hurlers syndrome
medicine
-
the enzyme is a target for enzyme replacement therapy of mucopolysaccharidosis type I patients
medicine
-
the enzyme is a target for enzyme replacement therapy of lysosomal storage disorders of mucopolysaccharidosis type I patients, the therapy depends on efficient uptake of recombinant enzyme into tissues of patients
medicine
-
the recombinant enzyme is used in enzyme relacement therapy of the Hurler form of mucopolysaccharidosis type I, MPSI, the enzyme is administered intraventricularly in to 31 Sprague-Dawley rat brains showing penetration of the brain and uptak into neurons and glial cells, rat tissue distribution of human recombinant enzyme activity, overview
medicine
-
administration of a high dose of the enzyme or development of a recombinant alpha-L-iduronidase containing many mannose 6-phosphate residues is required for further improvement of enzyme replacement therapy for skeletal disorders caused by mucopolysaccharidosis I
medicine
-
commercially available recombinant human laronidase (Aldurazyme) infusion is safe and effective in stabilizing or improving pulmonary function and physical endurance. Preclinical trials of the enzyme in the canine, dog and feline model and clinicial trials with affected patients with mucopolysaccharidosis type I
medicine
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as there is a difference in IDUA structural change between the severe mucopolysaccharidosis type I group and the attenuated one, except for a couple of mutations, structural analysis can help predict the clinical outcome of the disease
medicine
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the benefit of enzyme replacement therapy with recombinant laronidase before hematopoietic stem cell transplantation for mucopolysaccharidosis I is linked to improvement in patient's pretransplantation condition and thus tolerance of such intensive therapy. Short-term use of laronidase is not associated with increased risk of either graft-versus-host-disease or graft failure
medicine
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currently approved laronidase dose regimen, to treat the lysosomal storage disorder mucopolysaccharidosis type I, has similar efficacy and potentially improved safety compared to regimens using higher doses, regardless of dose frequency. The approved 0.58 mg/kg/week laronidase dose regimen provides near-maximal reductions in glycosaminoglycan storage and the best benefit-to-risk ratio. The 1.2 mg/kg every 2 weeks regimen may be an acceptable alternative for patients with difficulty receiving weekly infusions, but the long-term effects of this regimen are unknown. In general, laronidase therapy is safe and well tolerated in all treatment groups
medicine
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long-term clinical benefit and safety of laronidase in attenuated patients with mucopolysaccharidosis I. Laronidase effectively treats respiratory dysfunction, poor endurance, restricted mobility, hepatomegaly, and decreased quality of life. Prompt disease recognition and early and sustained treatment with laronidase will maximize these important benefits of treatment
medicine
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effectiveness of enzyme replacement therapy with laronidase on the range of motion of upper extremities and influence on activities of daily living of patients with mucopolysaccharidosis type I, MPS I, overview. MPS I has a spectrum of clinical severity, and is subdivided into three phenotypes: Hurler syndrome, that is severe, Hurler-Scheie syndrome, that is intermediate, and Scheie syndrome, that is attenuated
medicine
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the enzyme is useful in treatment of mucopolysaccharidosis type I, MPS I. In three patients with attenuated MPSA I, treated by laronidase, patients 2 and 3 display significant cognitive improvement within 2 years, and patients 1 and 3 display improvement, on MRI scans of the brain, overview
medicine
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the enzyme is useful in treatment of mucopolysaccharidosis type I, MPS I, by enzyme replacement therapy
medicine
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hIDUA is used for enzyme replacement therapy in MPS I patients
medicine
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intrathecal administration of recombinant human IDU, with potential dosing every 2-3 months, may provide benefit for the treatment of central nervous system disease in mucopolysaccharidosis type I patients
medicine
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a clone overexpressing the enzyme and, after encapsulation in alginate microcapsules, correcting MPS I human skin fibroblasts.These capsules can be surgically implanted in sites which are difficult to reach such as the brain of animal models and can be an approach for the treatment of MPS I and other lysosomal storage disorders
medicine
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alpha-L-iduronidase is used in enzyme replacement therapy approved for mucopolysaccharidosis type I treatment
pharmacology
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the enzyme is used in enzyme replacement therapy of mucopolysaccharidosis type I, MPSI, changes in hair morphology of MPSI patients treated with recombinant human enzyme, overview
pharmacology
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exploitation of alternative receptor systems that are independent of glycosylation but allow for efficient delivery to the lysosome