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Information on EC 4.2.3.12 - 6-pyruvoyltetrahydropterin synthase and Organism(s) Rattus norvegicus and UniProt Accession P27213
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4.2.3.12 6-pyruvoyltetrahydropterin synthaseIUBMB Comments
Catalyses triphosphate elimination and an intramolecular redox reaction in the presence of Mg2+. It has been identified in human liver. This enzyme is involved in the de novo synthesis of tetrahydrobiopterin from GTP, with the other enzymes involved being EC 1.1.1.153 (sepiapterin reductase) and EC 3.5.4.16 (GTP cyclohydrolase I) .
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Word Map
- 4.2.3.12
- phosphatases
-
protein-tyrosine
- phosphotyrosine
- src
- hyperphenylalaninemia
- bh4
- sepiapterin
- orthovanadate
-
dual-specificity
-
cyclohydrolase
- tcptp
- dihydropteridine
- vanadate
-
receptor-like
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receptor-type
-
phenylarsine
-
rfviii
- pterins
- ptp-pest
- ptp-1b
- 5-hydroxytryptophan
-
sulfenic
- pteridines
- ptpalpha
-
phosphotyrosyl
-
tyrosine-specific
-
thoracotomy
- phenylketonuria
- medicine
- ptpro
- gtpch
- haemophilia
-
substrate-trapping
- dystonia
- pervanadate
-
non-receptor
- csk
-
antigen-related
- ptpn22
- cdc25
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
ptps, 6-pyruvoyl-tetrahydropterin synthase, 6-pyruvoyltetrahydropterin synthase, ptp synthase, eptps, ptps-iii, pyruvoyltetrahydropterin synthase, sco 6650, 6-pyruvoyl tetrahydrobiopterin synthase, ptps homologue, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-amino-4-oxo-6-(erythro-1',2',3'-trihydroxypropyl)-7,8-dihydroxypterdine triphosphate lyase
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6-(1,2-dioxopropyl)tetrahydropterin synthase
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6-pyruvoyltetrahydropterin synthase
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6-pyruvoyltetrahydropterin synthase [16-cysteine] (human clone lamda HSY2 gene PCBD subunit)
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6-pyruvoyltetrahydropterin synthase [25-glutamine] (human clone lambdaHSY2 gene PCBD subunit)
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6-pyruvoyltetrahydropterin synthase [de-57-valine] (human clone lambdaHSY2 gene PCBD subunit)
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PPH4 synthase
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PPH4S
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protein purple
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PTP synthase
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PTPS
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pyruvoyltetrahydropterin synthase
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synthase, 6-pyruvoyltetrahydropterin
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synthase, 6-pyruvoyltetrahydropterin [16-cysteine] (human clone lamda HSY2 gene PCBD subunit)
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synthase, 6-pyruvoyltetrahydropterin [25-glutamine] (human clone lamdaHSY2 gene PCBD subunit)
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synthase, 6-pyruvoyltetrahydropterin [87-leucine] (human clone lamdaHSY2 gene PCBD subunit)
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synthase, 6-pyruvoyltetrahydropterin [de-57-valine] (human clone lambdaHSY2 gene PCBD subunit)
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
P-O bond cleavage
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intramolecular redox reaction
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triphosphate elimination
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cleavage of triphosphate bond
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SYSTEMATIC NAME
IUBMB Comments
7,8-dihydroneopterin 3'-triphosphate triphosphate-lyase (6-pyruvoyl-5,6,7,8-tetrahydropterin-forming)
Catalyses triphosphate elimination and an intramolecular redox reaction in the presence of Mg2+. It has been identified in human liver. This enzyme is involved in the de novo synthesis of tetrahydrobiopterin from GTP, with the other enzymes involved being EC 1.1.1.153 (sepiapterin reductase) and EC 3.5.4.16 (GTP cyclohydrolase I) [3].
CAS REGISTRY NUMBER
COMMENTARY
171716-27-1
synthase, 6-pyruvoyltetrahydropterin [16-cysteine] (human clone lamda HSY2 gene PCBD subunit) /6-pyruvoyltetrahydropterin synthase [16-cysteine] (human clone lambda HSY2 gene PCBD subunit)
171716-28-2
synthase, 6-pyruvoyltetrahydropterin [25-glutamine] (human clone lambdaHSY2 gene PCBD subunit) /6-pyruvoyltetrahydropterin synthase [25-glutamine] (human clone lambdaHSY2 gene PCBD subunit)
171716-29-3
synthase, 6-pyruvoyltetrahydropterin [de-57-valine] (human clone lambdaHSY2 gene PCBD subunit) /6-pyruvoyltetrahydropterin synthase [de-57-valine] (human clone lambdaHSY2 gene PCBD subunit)
171716-30-6
synthase, 6-pyruvoyltetrahydropterin [87-leucine] (human clone lambdaHSY2 gene PCBD subunit)
97089-82-2
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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
6-(L-erythro-1,2-dihydroxypropyl 3-monophosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + monophosphate
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the binding constant is 225fold increased with respect to the natural substrate
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?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
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-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
assay at
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?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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the enzyme is involved in tetrahydrobiopterin biosynthesis
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?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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the enzyme catalyzes the second step in the tetrahydrobiopterin biosynthetic pathway
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?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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the enzyme catalyzes the second step in the tetrahydrobiopterin biosynthetic pathway
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?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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the enzyme has six active sites located at the interface of three subunits. The enzyme contains an intersubunit catalytic triad motif composed of the amino acid residues Cys A42, His B89 and Asp B88 which is involved in the abstraction of protons from the substrate side-chain carbons. The gamma and beta phosphates of the substrate are essential for substrate binding and enhance the catalytic efficiency
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?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
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?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
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assay at
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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
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
assay at
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
-
assay at
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?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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the enzyme is involved in tetrahydrobiopterin biosynthesis
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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the enzyme catalyzes the second step in the tetrahydrobiopterin biosynthetic pathway
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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the enzyme catalyzes the second step in the tetrahydrobiopterin biosynthetic pathway
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
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the enzyme has six active sites located at the interface of three subunits. The enzyme contains an intersubunit catalytic triad motif composed of the amino acid residues Cys A42, His B89 and Asp B88 which is involved in the abstraction of protons from the substrate side-chain carbons. The gamma and beta phosphates of the substrate are essential for substrate binding and enhance the catalytic efficiency
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
bound to the Nepsilon-atoms of the three His residues HisA23, HisA48, and HisA50, one to each of the two active sites
Co2+
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free metal enzyme activity reaches 60% of activity of wild type with 0.50 mM and concentrations higher than 0.15 mM completely inactivates the enzyme. Less than 15% of activity with Mg2+ with 5 mM
Mg2+
Zn2+
additional information
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Cu2+, Fe2+, less than 15% of activity with Mg2+ with 5 mM of each ion
Mg2+
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free metal enzyme activity is 15% of the wild type with 8 mM, it is not bound to the enzyme
Zn2+
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free metal enzyme activity reaches 85% of activity of wild type with 0.05 mM and 8 mM Mg2+
Zn2+
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concentrations higher than 0.15 mM completely inactivates the enzyme
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-Vinylpyridine
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80% inactivation under non-denaturating and non-reducing conditions
additional information
NaCl 100 mM and KCl 100 mM have no effect on activity
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0091
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
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1.8
6-(L-erythro-1,2-dihydroxypropyl 3-monophosphate)-7,8-dihydropterin
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pH 7.4, 37ºC
0.008
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
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wild-type enzyme
0.008
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
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pH 7.4, 37ºC
5
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
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mutant enzyme E133Q
17.7
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
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mutant enzyme H89N
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
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
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). PTPS_RAT
144
0
16241
Swiss-Prot
Mitochondrion (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
17000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
each subunit consists of 144 residues with 2497 non-hydrogen atoms
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
mature protein lacks 4 N-terminal amino acids residues
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C42A
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no catalytic activity, complete loss of metal binding site and activity, it is the only Cys in the active site
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, hydroxyapatite column, butyl-toyopearl chromatography, gel filtration, HPLC ion exchange column
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed as maltose-binding-6-pyruvoyl-tetrahydropterin-synthase fusion protein
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Thny, B.; Leimbacher, W.; Blau, N.; Heizmann, C.W.; Burgisser, D.
Human liver 6-pyruvoyl-tetrahydropterin synthase: expression of the cDNA, purification and preliminary characterization of the recombinant protein
Adv. Exp. Med. Biol.
338
187-190
1993
Homo sapiens, Rattus norvegicus
Burgisser, D.M.; Thny, B.; Redweik, U.; Hess, D.; Heizmann, C.W.; Huber, R.; Nar, H.
6-Pyruvoyl tetrahydropterin synthase, an enzyme with a novel type of active site involving both zinc binding and an intersubunit catalytic triad motif. Site-directed mutagenesis of the proposed active center, characterization of the metal binding site and modeling of substrate binding
J. Mol. Biol.
253
358-369
1995
Rattus norvegicus
Auerbach, G.; Nar, H.
The pathway from GTP to tetrahydropterin: three-dimensional structures of GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase
Biol. Chem.
378
185-192
1997
Bombyx mori, Bos taurus, Drosophila melanogaster, Homo sapiens, Rattus norvegicus (P27213)
Burgisser, D.M.; Thny, B.; Redweik, U.; Hunziker, P.; Heizmann, C.W.; Blau, N.
Expression and characterization of recombinant human and rat liver 6-pyruvoyl tetrahydropterin synthase. Modified cysteine residues inhibit the enzyme activity
Eur. J. Biochem.
219
497-502
1994
Homo sapiens, Rattus norvegicus
Inoue, Y.; Kawasaki, Y.; Harada, T.; Hatekeyama, K.; Kagamiyama, H.
Purification and cDNA cloning of rat 6-pyruvoyl-tetrahydropterin synthase
J. Biol. Chem.
266
20791-20796
1991
Rattus norvegicus (P27213)
Ploom, T.; Thony, B.; Yim, J.; Lee, S.; Nar, H.; Leimbacher, W.; Richardson, J.; Huber, R.; Auerbach, G.
Crystallographic and kinetic investigations on the mechanism of 6-pyruvoyl tetrahydropterin synthase
J. Mol. Biol.
286
851-860
1999
Rattus norvegicus
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