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Information on EC 4.2.1.96 - 4a-hydroxytetrahydrobiopterin dehydratase and Organism(s) Rattus norvegicus and UniProt Accession P61459
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4.2.1.96 4a-hydroxytetrahydrobiopterin dehydrataseIUBMB Comments
In concert with EC 1.5.1.34, 6,7-dihydropteridine reductase, the enzyme recycles 4a-hydroxytetrahydrobiopterin back to tetrahydrobiopterin, a cosubstrate for several enzymes, including aromatic amino acid hydroxylases. The enzyme is bifunctional, and also acts as a dimerization cofactor of hepatocyte nuclear factor-1alpha (HNF-1).
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Word Map
- 4.2.1.96
- pterins
- hyperphenylalaninemias
- dihydropteridine
- bh4
- hydroxylases
-
cyclohydrolase
-
7-biopterin
- 6-pyruvoyl-tetrahydropterin
- vitiligo
-
hnf1alpha
- sepiapterin
- tetrahydropterins
-
depigmentation
- gtpch
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
pcd/dcoh, pterin-4a-carbinolamine dehydratase, dcoh/pcd, dcoh2, dcohalpha, xdcoh, 4a-carbinolamine dehydratase, pterin-4alpha-carbinolamine dehydratase, pterin-4 alpha-carbinolamine dehydratase, cdcoh, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
4 alpha-Hydroxy-tetrahydropterin dehydratase
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4-alpha-hydroxy-tetrahydropterin dehydratase
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4a-Carbinolamine dehydratase
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4a-Hydroxytetrahydrobiopterin dehydratase
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4a-Hydroxytetrahydropterin dehydratase
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cDcoH
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DCoH
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DCoH/PCD
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Dehydratase, 4a-carbinolamine
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Dimerization cofactor of hepatocyte nuclear factor 1-alpha
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Dimerization cofactor of HNF1
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Dimerization factor of HNF1/pterin-4alpha-carbinolamine dehydratase
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GenBank AE000671-derived protein GI 2982796
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P4aCD
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PCD
PCD/DCoH
PCD/PhhB
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PCDH
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Phenylalanine hydroxylase-stimulating protein
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Phenylalanine hydroxylase-stimulating protein/pterin-4alpha-carbinolamine dehydratase
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PHS
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PHS/PCD
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Pterin carbinolamine dehydratase
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Pterin-4 alpha-carbinolamine dehydratase
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Pterin-4-alpha-carbinolamine dehydratase
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Pterin-4a-carbinolamine dehydratase
Pterin-4a-carbinolamine dehydratase (Aquifex aeolicus gene phhB)
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Pterin-4a-carbinolamine dehydratase/dimerization cofactor of HNF1
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Pterin-4alpha-carbinolamine dehydratase
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Pterin-4alpha-carbinolamine dehydratase (PCD)/dimerization cofactor for the transcription factor HBF-1alpha
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XDCoH
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additional information
PCD
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PCD/DCoH
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Pterin-4a-carbinolamine dehydratase
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additional information
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the enzyme has identical amino acid sequence to DCoH, the dimerization cofactor of the transcription regulator, HNF-1alpha
additional information
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the enzyme is identical with the dimerization cofactor DCoH, a cofactor for the hepatocyte nuclear factor 1alpha, HNF1alpha, which is essential for expression of phenylalanine hydroxylase PAH EC 1.14.16.1
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
4a-hydroxytetrahydrobiopterin = 6,7-dihydrobiopterin + H2O
His61 and His79 act as acid catalysts for the stereospecific elimination of the 4a(R)- and 4a(S)-hydroxyl groups, respectively. The role of His62 is primarily binding substrate with additional component of base catalysis
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
elimination of H2O
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-
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SYSTEMATIC NAME
IUBMB Comments
4a-hydroxytetrahydrobiopterin hydro-lyase (6,7-dihydrobiopterin-forming)
In concert with EC 1.5.1.34, 6,7-dihydropteridine reductase, the enzyme recycles 4a-hydroxytetrahydrobiopterin back to tetrahydrobiopterin, a cosubstrate for several enzymes, including aromatic amino acid hydroxylases. The enzyme is bifunctional, and also acts as a dimerization cofactor of hepatocyte nuclear factor-1alpha (HNF-1).
CAS REGISTRY NUMBER
COMMENTARY
204788-56-7
pterin-4a-carbinolamine dehydratase (Aquifex aeolicus gene phhB), genBank AE000671-derived protein GI 2982796
87683-70-3
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4a(R)-hydroxy-6(S)-methyltetrahydropterin
quinoid 6(S)-methyldihydropterin
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-
-
?
4a(S)-hydroxy-6(R)-methyltetrahydropterin
quinoid 6(R)-methyldihydropterin
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-
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?
4a-Hydroxy-6(S)-methyltetrahydropterin
Quinoid 6(S)-methyldihydropterin
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-
-
?
(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
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-
-
?
4a(R)-hydroxy-6(S)-propyltetrahydropterin
quinoid 6(S)-propyldihydropterin
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-
-
-
?
4a-Hydroxy-6(S)-methyltetrahydropterin
Quinoid 6(S)-methyldihydropterin
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?
4a-Hydroxy-6(S)-propyltetrahydropterin
Quinoid 6(S)-propyldihydropterin
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?
additional information
?
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the enzyme may not play an important role in the regulation of the synthesis of those neurotransmitters which are derived from the hydroxylated aromatic amino acids
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?
additional information
?
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the enzyme is essential in vivo to prevent rearrangement of 4a-hydroxy-6(R)-tetrahydrobiopterin and to maintain the supply of tetrahydrobiopterin cofactor for hydroxylases under conditions where the nonenzymatic rate would be inadequate
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?
additional information
?
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the cytosolic enzyme is involved in the regeneration of tetrahydrobiopterin, the cofactor of aromatic amino acid monooxygenases
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?
additional information
?
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the enzyme is essentially identical to a cofactor that regulates dimerization of a nuclear homeodomain-containing protein involved in transcription
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?
additional information
?
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enzyme plays a role in the regulation of expression of phenylalanine hydroxylase via transcription factor HNF1alpha
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
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the enzyme may not play an important role in the regulation of the synthesis of those neurotransmitters which are derived from the hydroxylated aromatic amino acids
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?
additional information
?
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the enzyme is essential in vivo to prevent rearrangement of 4a-hydroxy-6(R)-tetrahydrobiopterin and to maintain the supply of tetrahydrobiopterin cofactor for hydroxylases under conditions where the nonenzymatic rate would be inadequate
-
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?
additional information
?
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the cytosolic enzyme is involved in the regeneration of tetrahydrobiopterin, the cofactor of aromatic amino acid monooxygenases
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?
additional information
?
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-
the enzyme is essentially identical to a cofactor that regulates dimerization of a nuclear homeodomain-containing protein involved in transcription
-
-
?
additional information
?
-
-
enzyme plays a role in the regulation of expression of phenylalanine hydroxylase via transcription factor HNF1alpha
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
diethyldicarbonate
inactivation is complete when about 1.2 His per subunit are derivatized
glycerol
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dietary glycerol leads to a small reduction in the mRNA level of the enzyme PCD/DCoH only in the liver, not in kidney, 40% glycerol diet lead to 2.5fold reduced activity in liver cytosol
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
glycerol
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leads to a slight increase in enzyme activity only in the kidney, not in liver, when feeded as a 40% glycerol diet
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
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the PCD activity of the homoteterameric enzyme is involved in the aromatic amino acid metabolism
physiological function
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the bifunctional protein shows two disparate functions, i.e. dimerization cofactor of HNF-1, DCoH1, and pterin-4a-carbinolamine dehydratase, PCD, that are associated with a change in oligomeric state between dimer and tetramer, overview. The PCD activity of homotetramers aids in aromatic amino acidmetabolism
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). PHS_RAT
104
0
12000
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
11800
4 * 11800, mutant enzyme H61A, H62A and H79A, electrospray mass spectrometry
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
tetramer
4 * 11800, mutant enzyme H61A, H62A and H79A, electrospray mass spectrometry
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinnat detagged mutant T51S enzyme, 13 mg/ml protein from 0.1 M HEPES-Na, pH 7.5, 2% v/v PEG 400, and 2.0 M ammonium sulfate, X-ray diffraction structure determination and analysis at 1.8 A resolution
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H61A
mutant enzyme H61A shows no dehydratase activity with 4a(R)-hydroxy-6(R)-methyltetrahydropterin. Mutant enzyme H79A shows no dehydratase activity with 4a(S)-hydroxy-6(R)-methyltetrahydropterin. The Km-value for 4a(S)-hydroxy-6(R)-methyltetrahydropterin is comparable to the Km-value of the wild type enzyme. The turnover number of the mutant enzyme H62A is 24% of that with the wild type enzyme for the 4a(R),6(S)-isomer and the 4a(S),6(R)-isomer
T51S
-
the point mutation at the enzyme tetramer interface overcomes the dissociation barrier of the homotetramer and increases the interaction with HNF-1alpha. Presence of an ordered water molecule at the tetramer interface, which may destabilize the homotetramer
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged enzyme from Escherichia coli by glutathione affinity chromatography, tag cleavage by thrombin, and p-aminobenzamidine affinity chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
DCoH2 unfolding through guanidine is reversible, kinetics, equilibrium unfolding data fit to a two-state model with no apparent intermediate, but folding intermediates are detectable. Proposal of an unfolding pathway in which the tetramer unfolds slowly, but the dimer folds reversibly
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hauer, C.R.; Rebrin, I.; Thoeny, B.; Neuheiser, F.; Curtius, H.C.; Hunziker, P.; Blau, N.; Ghisla, S.; Heizmann, C.W.
Phenylalanine hydoxylase-stimulating protein/pterin-4alpha-carbinolamine dehydratase from rat and human liver
J. Biol. Chem.
268
4828-4831
1993
Homo sapiens, Rattus norvegicus
Ficner, R.; Sauer, U.H.; Stier, G.; Suck, D.
Three-dimensional structure of the bifunctional protein PCH/DCoH, a cytoplasmic enzyme interacting with transcription factor HNF1
EMBO J.
14
2034-2042
1995
Rattus norvegicus
Kster, S.; Stier, G.; Ficner, R.; Hoezer, M.; Curtius, H.C.; Suck, D.; Ghisla, S.
Location of the active site and proposed catalytic mechanism of pterin-4alpha-carbinolamine dehydratase
Eur. J. Biochem.
241
858-864
1996
Homo sapiens, Rattus norvegicus
Davis, M.D.; Kaufman, S.; Milstien, S.
Distribution of 4a-hydroxytetrahydropterin dehydratase in rat tissues
FEBS Lett.
302
73-76
1992
Rattus norvegicus
Ficner, R.; Sauer, U.H.; Ceska, T.A.; Stier, G.; Suck, D.
Crystallization and preliminary crystallographic studies of recombinant dimerization cofactor of transcription factor HNF1/pterin-4alpha-carbinolamine dehydratase from liver
FEBS Lett.
357
62-64
1995
Rattus norvegicus
Rebrin, I.; Bailey, S.W.; Boerth, S.R.; Ardell, M.D.; Ayling, J.E.
Catalytic characterization of 4alpha-hydroxytetrahydropterin dehydratase
Biochemistry
34
5801-5810
1995
Rattus norvegicus
Kim, J.L.; Burley, S.K.; Hughes, H.
PCH/DCoH: more than a second molecular saddle
Curr. Biol.
3
531-534
1995
Rattus norvegicus
Rebrin, I.; Thoeny, B.; Bailey, S.W.; Ayling, J.E.
Stereospecificity and catalytic function of histidine residues in 4alpha-hydroxy-tetrahydropterin dehydratase/DCoH
Biochemistry
37
11246-11254
1998
Rattus norvegicus (P61459)
Connolly, E.; Donlon, J.
Effects of dietary glycerol on the expression of pterin carbinolamine dehydratase in the rat
Biochem. J.
373
993-997
2003
Rattus norvegicus
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