Information on EC 4.2.1.96 - 4a-hydroxytetrahydrobiopterin dehydratase and Organism(s) Homo sapiens

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
4.2.1.96
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RECOMMENDED NAME
GeneOntology No.
4a-hydroxytetrahydrobiopterin dehydratase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(6R)-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin = (6R)-6-(L-erythro-1,2-dihydroxypropyl)-7,8-dihydro-6H-pterin + H2O
show the reaction diagram
the mechanism of dehydration involves base catalysis at the N(5)-H group of the substrate by His61
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
elimination of H2O
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
L-phenylalanine degradation I (aerobic)
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L-phenylalanine degradation V
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phenylalanine metabolism
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Folate biosynthesis
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
(6R)-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin hydro-lyase [(6R)-6-(L-erythro-1,2-dihydroxypropyl)-7,8-dihydro-6H-pterin-forming]
Catalyses the dehydration of 4a-hydroxytetrahydrobiopterins
CAS REGISTRY NUMBER
COMMENTARY hide
204788-56-7
pterin-4a-carbinolamine dehydratase (Aquifex aeolicus gene phhB), genBank AE000671-derived protein GI 2982796
87683-70-3
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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PCD deficiency causes in newborns a mild form of hyperphenylalaninaemia with persistent high urinary levels of primapterin. Affected patients appear completely normal, but have elevated phenylalanine levels at birth, which normalize after few months of life and remain normal or just above the normal range of phenylalanine with an unrestricted diet
physiological function
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PCD is required for the regeneration of tetrahydrobiopterin after phenylalanine hydroxylation. PCD can dimerize with HNF-1a and work as a transcription factor
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(6R)-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin
(6R)-6-(L-erythro-1,2-dihydroxypropyl)-7,8-dihydro-6H-pterin + H2O
show the reaction diagram
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-
-
?
4a-Hydroxy-6(S)-methyltetrahydropterin
Quinoid 6(S)-methyldihydropterin
show the reaction diagram
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-
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4a-Hydroxy-6(S)-propyltetrahydropterin
Quinoid 6(S)-propyldihydropterin
show the reaction diagram
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-
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-
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4a-hydroxy-tetrahydrobiopterin
7,8-dihydrobiopterin + H2O
show the reaction diagram
4a-hydroxy-tetrahydropterin
7,8-dihydropterin + H2O
show the reaction diagram
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-
-
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4a-hydroxytetrahydrobiopterin
?
show the reaction diagram
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-
-
-
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4alpha-hydroxy-6(S)-methyltetrahydropterin
?
show the reaction diagram
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-
-
-
?
6,6-dimethyl-4a-hydroxy-tetrahydropterin
6,6-dimethyl-7,8-dihydropterin + H2O
show the reaction diagram
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pterin-4alpha-carbinolamine
quininoid dihydropterin + H2O
show the reaction diagram
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?
additional information
?
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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
additional information
?
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.004 - 0.0053
(6R)-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin
0.003
4a-Hydroxy-6(S)-methyltetrahydropterin
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10°C, pH 7.4
0.0013
4a-Hydroxy-6(S)-propyltetrahydropterin
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fetal and adult enzyme
0.0047 - 0.0052
4a-hydroxytetrahydrobiopterin
0.007 - 2.2
6(S)-methyl-7,8-dihydropterin-4a-carbinolamine
additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
23 - 24
(6R)-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4a-hydroxypterin
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
Q9H0N5
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
11000
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4 * 11000, SDS-PAGE
12000
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4 * 12000, SDS-PAGE
12675
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4 * 12675, mutant enzyme C81S, electrospray-ionisation mass spectrometry
12690
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4 * 12690, wild type enzyme, electrospray-ionisation mass spectrometry
12744
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4 * 12744, mutant C81R, electrospray-ionisation mass spectrometry
45000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
no decrease in activity upon dilution and storage at 4°C
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, stable
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mutant proteins require the inclusion of 10% glycerol in the storage buffer to maintain solubility
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant
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wild type and mutant enzymes Cys81Ser and Cys81Arg
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli BL21(DE3)pLysS
the 18 amino acid-truncated mutant E87T cannot be overexpressed in Escherichia coli; wild type and mutant enzyme C82R overexpressed in Escherichia coli
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wild-type and mutant enzymes
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C81R
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mutant enzyme Cys81Arg has significantly lower activity
E57A
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the His79Ala mutant and the His79Ser mutant exhibit about 40% the activity of the wild-type enzyme. In the mutant enzymes His61Ala and His62Ala the activity is reduced to 10%. In the mutant enzymes Asp60Ala and Arg87Ala the activity is reduced to 30%. The Glu57Ala mutant and the His61Ala,His62Ala double mutant show no activity
E97K
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a biopsy of duodenal mucosa from a patient with homozygous E97K mutation has 17% of normal activity
H61A
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the His79Ala mutant and the His79Ser mutant exhibit about 40% the activity of the wild-type enzyme. In the mutant enzymes His61Ala and His62Ala the activity is reduced to 10%. In the mutant enzymes Asp60Ala and Arg87Ala the activity is reduced to 30%. The Glu57Ala mutant and the His61Ala,His62Ala double mutant show no activity
H61A/H62A
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the His79Ala mutant and the His79Ser mutant exhibit about 40% the activity of the wild-type enzyme. In the mutant enzymes His61Ala and His62Ala the activity is reduced to 10%. In the mutant enzymes Asp60Ala and Arg87Ala the activity is reduced to 30%. The Glu57Ala mutant and the His61Ala,His62Ala double mutant show no activity
H62A
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the His79Ala mutant and the His79Ser mutant exhibit about 40% the activity of the wild-type enzyme. In the mutant enzymes His61Ala and His62Ala the activity is reduced to 10%. In the mutant enzymes Asp60Ala and Arg87Ala the activity is reduced to 30%. The Glu57Ala mutant and the His61Ala,His62Ala double mutant show no activity
H79A
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the His79Ala mutant and the His79Ser mutant exhibit about 40% the activity of the wild-type enzyme. In the mutant enzymes His61Ala and His62Ala the activity is reduced to 10%. In the mutant enzymes Asp60Ala and Arg87Ala the activity is reduced to 30%. The Glu57Ala mutant and the His61Ala,His62Ala double mutant show no activity
H79S
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the His79Ala mutant and the His79Ser mutant exhibit about 40% the activity of the wild-type enzyme. In the mutant enzymes His61Ala and His62Ala the activity is reduced to 10%. In the mutant enzymes Asp60Ala and Arg87Ala the activity is reduced to 30%. The Glu57Ala mutant and the His61Ala,His62Ala double mutant show no activity
N61D
The decreased ability of the N61D mutant to affect HNF1alpha-dependent DNA binding is likely a direct result of altered quaternary structure.
N61D/Q45R/K98Q
site-directed mutagenesis, triple DCoHa mutant (Q45R/K98Q/N61D) is unable to affect HNF1alpha-dependent DNA binding in vitro.
Q45R/K98Q
mutant Q45R/K98Q is not able to affect HNF1alpha-dependent DNA binding in vitro
additional information