Information on EC 3.2.1.76 - L-iduronidase

New: Word Map on EC 3.2.1.76
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Search Reference ID:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY hide
3.2.1.76
-
RECOMMENDED NAME
GeneOntology No.
L-iduronidase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
hydrolysis of unsulfated alpha-L-iduronosidic linkages in dermatan sulfate
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Glycosaminoglycan degradation
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
glycosaminoglycan alpha-L-iduronohydrolase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9073-56-7
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
physiological function
-
the enzyme is involved in the degradation of the glycosaminoglycans dermatan sulfate and heparan sulfate
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) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
4-methylumbelliferol + 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
?
show the reaction diagram
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-1,4)-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
-
-
-
-
?
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
-
-
?
phenyl alpha-L-iduronide + H2O
?
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
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
-
-
-
D-saccharolactone
-
-
EDTA
-
competitive, equal inhibition of enzyme from healthy individuals and mucopolysaccharidosis type I patients
Fe3+
-
-
p-chloromercuribenzoate
-
-
SO42-
-
-
[(2S,3R,4R)-3,4-dihydroxy-5-oxotetrahydrofuran-2-yl](hydroxy)acetic acid
-
competitive inhibitor
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
-
dithiothreitol
-
-
glutathione
-
-
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.031 - 0.3
4-Methylumbelliferyl alpha-L-iduronide
0.015 - 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 - 0.14
alpha-L-iduronisyl-(alpha-1,4)2,5-anhydro-D-mannitol
0.01 - 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 - 0.003
IdoA-GlcNAc6S-IdoA2S-anM6S
0.002
IdoA-GlcNS6S-IdoA2S-anM6S
-
pH 4.8
-
0.2 - 1.5
phenyl alpha-L-iduronide
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.83
5-fluoro-alpha-L-idopyranosyluronic acid fluoride
Homo sapiens
-
pH 4.5, 37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5
(5R,6R,7S,8S)-5,6,7,8-tetrahydro-6,7,8-trihydroxytetrazolo[1,2-a]pyridine-5-carboxylate
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 hide
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 hide
LITERATURE
3 - 3.5
3.4
-
assay at
4.2
-
assay at
4.4
-
anhydromannitol iduronide as substrate
5.8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3.5 - 7.5
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
21
-
assay at
22 - 37
-
assay at
32
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
moderate activity
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
-
low activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
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
-
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
65000
-
gel filtration, form I and II from liver
67000
-
gel filtration, L-iduronidase II
68000
-
gel filtration, soluble form
69000
-
Western blot analysis, mature component after incorporation into cells
70000
-
gel filtration
76000
-
Western blot analysis, mature component after incorporation into cells
79000
SDS-PAGE
83000
-
Western blot analysis, before incorporation into cells
85000
-
gel filtration, membrane associated form
87000
-
gel filtration, L-iduronidase I
480000
-
gel filtration and native PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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 hide
LITERATURE
glycoprotein
phosphoprotein
-
phosphorylations on S59 and S482, phosphatase treatment
proteolytic modification
side-chain modification
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 hide
LITERATURE
3
-
rapidly inactivated
171560
8
-
rapidly inactivated
171560
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50
-
enzyme from mucopolysaccharidosis patients is more stable than enzyme from healthy individuals
55
-
both forms are stable over 30 min
65
-
L-iduronidase II is more labile
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 hide
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
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 Cos-1 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
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 hide
LITERATURE
134del12
-
homozygous genotype with only residual enzyme activity
A160D
-
severe mucopolysaccharidosis type I phenotype
A319V
-
attenuated mucopolysaccharidosis type I phenotype
A327P/R383H
-
a genotype with only residual enzyme activity
A75T
-
severe mucopolysaccharidosis type I phenotype
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
D349Y
-
severe mucopolysaccharidosis type I phenotype
E178K
-
intermediate mucopolysaccharidosis type I phenotype
E182A
-
catalytically inactive
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
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
N350I
-
attenuated mucopolysaccharidosis type I phenotype
P183R
-
severe mucopolysaccharidosis type I phenotype
P496L
-
intermediate mucopolysaccharidosis type I phenotype
P496R
-
severe mucopolysaccharidosis type I phenotype
Q584X
-
the missense mutation is associated with mucopolysaccharidosis type I
Q60X
-
the missense mutation is associated with mucopolysaccharidosis type I
Q70X/R383H
-
a genotype with only residual enzyme activity
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
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
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
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
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
Y343X
-
the missense mutation is associated with mucopolysaccharidosis type I
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
pharmacology