Information on EC 4.2.3.12 - 6-pyruvoyltetrahydropterin synthase

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

EC NUMBER
COMMENTARY
4.2.3.12
-
RECOMMENDED NAME
GeneOntology No.
6-pyruvoyltetrahydropterin synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
7,8-dihydroneopterin 3'-triphosphate = 6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
catalyses triphosphate elimination and an intramolecular redox reaction in the presence of Mg2+. Identified in human liver. The product is 6-pyruvoyltetrahydrobiopterin
-
-
-
7,8-dihydroneopterin 3'-triphosphate = 6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
mechanism
-
7,8-dihydroneopterin 3'-triphosphate = 6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
the enzyme catalyzes the elimination of triphosphate as well as a series of tautomerization reactions. Incorporation of protons into positions C6 and C3' of the product
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
cleavage of triphosphate bond
-
-
-
-
intramolecular redox reaction
-
-
-
-
P-O bond cleavage
-
-
-
-
triphosphate elimination
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
drosopterin and aurodrosopterin biosynthesis
-
Folate biosynthesis
-
Metabolic pathways
-
tetrahydrobiopterin biosynthesis I
-
tetrahydrobiopterin biosynthesis II
-
tetrahydrobiopterin biosynthesis III
-
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].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
2-amino-4-oxo-6-(erythro-1',2',3'-trihydroxypropyl)-7,8-dihydroxypterdine triphosphate lyase
-
-
-
-
6-(1,2-dioxopropyl)tetrahydropterin synthase
-
-
-
-
6-carboxy-5,6,7,8-tetrahydropterin synthase
-
6-pyruvoyl-5,6,7,8-tetrahydropterin synthase homologue, gene QueD
6-pyruvoyl tetrahydrobiopterin synthase
-
-
6-pyruvoyl-tetrahydropterin synthase
-
-
6-pyruvoyl-tetrahydropterin synthase
-
-
6-pyruvoyl-tetrahydropterin synthase
-
-
6-pyruvoyltetrahydropterin synthase
-
-
-
-
6-pyruvoyltetrahydropterin synthase
-
-
6-pyruvoyltetrahydropterin synthase
-
-
6-pyruvoyltetrahydropterin synthase
-
-
6-pyruvoyltetrahydropterin synthase paralog
-
-
6-pyruvoyltetrahydropterin synthase [16-cysteine] (human clone lamda HSY2 gene PCBD subunit)
-
-
-
-
6-pyruvoyltetrahydropterin synthase [25-glutamine] (human clone lambdaHSY2 gene PCBD subunit)
-
-
-
-
6-pyruvoyltetrahydropterin synthase [de-57-valine] (human clone lambdaHSY2 gene PCBD subunit)
-
-
-
-
6-pyruvoyltetrahydropterin synthase-like protein
-
-
EC 4.6.1.10
-
-
formerly
-
PPH4 synthase
-
-
-
-
PPH4S
-
-
-
-
protein purple
-
-
-
-
PTP synthase
-
-
-
-
PTPS
-
-
-
-
PTPS
G3FNL7
-
PTPS homologue
-
-
pyruvoyltetrahydropterin synthase
-
-
-
-
synthase, 6-pyruvoyltetrahydropterin
-
-
-
-
synthase, 6-pyruvoyltetrahydropterin [16-cysteine] (human clone lamda HSY2 gene PCBD subunit)
-
-
-
-
synthase, 6-pyruvoyltetrahydropterin [25-glutamine] (human clone lamdaHSY2 gene PCBD subunit)
-
-
-
-
synthase, 6-pyruvoyltetrahydropterin [87-leucine] (human clone lamdaHSY2 gene PCBD subunit)
-
-
-
-
synthase, 6-pyruvoyltetrahydropterin [de-57-valine] (human clone lambdaHSY2 gene PCBD subunit)
-
-
-
-
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 lamda HSY2 gene PCBD subunit)
171716-28-2
synthase, 6-pyruvoyltetrahydropterin [25-glutamine] (human clone lamdaHSY2 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 lamdaHSY2 gene PCBD subunit)
97089-82-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
silkworm
-
-
Manually annotated by BRENDA team
-
Q03393
SwissProt
Manually annotated by BRENDA team
cloned in Escherichia coli
Q03393
SwissProt
Manually annotated by BRENDA team
transgenic mouse with a replacement of the Pts allele, encoding the 6-pyruvoyl-tetrahydropterin synthase, by an in-frame insertion in exon 2 with the beta-galactosidase gene generating a fusion protein containing the N-terminal 35 amino acids for 6-pyruvoyl-tetrahydropterin synthase followed by the beta-galactosidase
-
-
Manually annotated by BRENDA team
cloned in Escherichia coli
-
-
Manually annotated by BRENDA team
Wistar rat
-
-
Manually annotated by BRENDA team
Wistar, cloned
SwissProt
Manually annotated by BRENDA team
strain PCC 7942
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1'-3H-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
tritium released is not incorporated in the product
-
?
2'-3H-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
tritium released is not incorporated in the product
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-monophosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + monophosphate
show the reaction diagram
-
the binding constant is 225fold increased with respect to the natural substrate
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
Q03393
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
C6KTB6
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-, one of the enzymes 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
show the reaction diagram
Q03393
23 bp exon 3 skipping in transcription rather than post-transcriptional mechanisms is a major cause of the low PTPS protein expression in human macrophages and related cell types. The exon lacking leads to a premature stop codon encoding for a shorter protein instead of the full-length functional enzyme
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
rate-limiting enzyme in the synthesis of human tetrahydrobiopterin
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
the enzyme catalyzes the first step in the conversion of 7,8-dihydroneopterin triphosphate to tetrahydrobiopterin
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
Q03393
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
the enzyme catalyzes the second step in the tetrahydrobiopterin biosynthetic pathway, 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
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
the enzyme is post-translationally phosphorylated in several Ser residues by protein kinases. The enzyme requires the phosphoserine 19 residue for maximal activity under in vivo conditions. Mutant enzymes with alterations in the protein kinase recognition site, phosphoserine 19 residue, are not phosphorylated by protein kinase and have reduced activity
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
the enzyme catalyzes the second step of tetrahydrobiopterin (BH4) synthesis
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
?
show the reaction diagram
-
the second of the three enzymatic steps in the synthesis of tetrahydrobiopterin from GTP
-
-
?
6-pyruvoyltetrahydropterin
6-carboxy-5,6,7,8-tetrahydropterin + ?
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
Q03393
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
P27213
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
G3FNL7, -
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
Q03393
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
P27213
assay at
-
?
sepiapterin
7,8-dihydropterin
show the reaction diagram
-
-
-
?
sepiapterin
7,8-dihydropterin
show the reaction diagram
-
the enzyme cleaves the C6 side chain of sepiapterin, sepiapterin side chain releasing activity, SSCR activity
-
?
sepiapterin
6-carboxy-5,6,7,8-tetrahydropterin + ?
show the reaction diagram
-
-
-
-
?
dihydroneopterin triphosphate
6-hydroxymethyldihydropterin + triphosphate + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the sequence of reaction steps include redox transfer between atoms N5, C6 and C1' and unusual triphosphate elimination at the C2'-C3' bond in the side chain
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
one of the enzymes 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
show the reaction diagram
Q03393
23 bp exon 3 skipping in transcription rather than post-transcriptional mechanisms is a major cause of the low PTPS protein expression in human macrophages and related cell types. The exon lacking leads to a premature stop codon encoding for a shorter protein instead of the full-length functional enzyme
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
rate-limiting enzyme in the synthesis of human tetrahydrobiopterin
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
the enzyme catalyzes the first step in the conversion of 7,8-dihydroneopterin triphosphate to tetrahydrobiopterin
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
Q03393
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
the enzyme catalyzes the second step in the tetrahydrobiopterin biosynthetic pathway, 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
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
the enzyme is post-translationally phosphorylated in several Ser residues by protein kinases. The enzyme requires the phosphoserine 19 residue for maximal activity under in vivo conditions. Mutant enzymes with alterations in the protein kinase recognition site, phosphoserine 19 residue, are not phosphorylated by protein kinase and have reduced activity
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
6-(1,2-dioxopropyl)-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
the enzyme catalyzes the second step of tetrahydrobiopterin (BH4) synthesis
-
-
?
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
?
show the reaction diagram
-
the second of the three enzymatic steps in the synthesis of tetrahydrobiopterin from GTP
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
-
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
Q03393
assay at
-
?
7,8-dihydroneopterin triphosphate
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
show the reaction diagram
P27213
assay at
-
?
additional information
?
-
-
the sequence of reaction steps include redox transfer between atoms N5, C6 and C1' and unusual triphosphate elimination at the C2'-C3' bond in the side chain
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NADPH
-
required
additional information
-
no cofactor required
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ba2+
-
stimulatory effect, 5 mM greatly accelerates activity
Ca2+
-
less than 15% of activity with Mg2+ with 5 mM
Ca2+
-
stimulatory effect and additive effect at Mg2+, 1 mM
Ca2+
P27213
65% of the activity with equal concentration of Mg2+
Co2+
-
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+
-
free metal enzyme activity is 15% of the wild type with 8 mM, it is not bound to the enzyme
Mg2+
-
necessary for activity; required
Mg2+
Q03393
necessary for activity
Mg2+
-
stimulates, Km of 0.2 mM and 2 mM at pH 8.5 and 37C
Mg2+
P27213
optimum concentration is 8 mM
Mg2+
G3FNL7, -
75% enhancement
Mn2+
-
less than 15% of activity with Mg2+ with 5 mM
Ni2+
-
71% of the activity with Mg2+ with NiCl2, 5 mM
Ni2+
-
no effect on enzyme activity
Sr2+
-
5 mM greatly accelerates activity
Zn2+
-
bound to the enzyme; concentrations higher than 0.15 mM completely inactivates the enzyme; free metal enzyme activity reaches 85% of activity of wild type with 0.05 mM and 8 mM Mg2+; the zinc/enzyme-subunit ratio of the wild-type enzyme is 0.8
Zn2+
P27213
bound to the Nepsilon-atoms of the three His residues HisA23, HisA48, and HisA50, one to each of the two active sites
Zn2+
-
no effect on enzyme activity
Mn2+
-
stimulatory effect but additional competitive or inhibitory effect
additional information
-
Cu2+, Fe2+, less than 15% of activity with Mg2+ with 5 mM of each ion
additional information
-
Cu2+ has no effect on activity
additional information
-
no metal ion required
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
4-Vinylpyridine
-
95% inactivation under non-denaturating and non-reducing conditions
4-Vinylpyridine
-
80% inactivation under non-denaturating and non-reducing conditions
ammonium sulfate
P27213
50% inactivation at 400 mM
Ca2+
-
10 mM, 40-100% inhibition
Co2+
-
10 mM, 40-100% inhibition
Co2+
G3FNL7, -
complete inhibition
Cu2+
-
10 mM, 40-100% inhibition
Cu2+
G3FNL7, -
complete inhibition
EDTA
-
completely inactivates the enzyme by complexation of Mg2+
EDTA
-
above 10 mM
Fe2+
G3FNL7, -
slight inhibition
-
Mg2+
-
10 mM, 40-100% inhibition
Mn2+
-
10 mM, 40-100% inhibition
Mn2+
G3FNL7, -
complete inhibition
N-(7-Dimethyl-amino-4-methyl coumarinyl) maleimide
-
-
Ni2+
-
10 mM, 40-100% inhibition
Zn2+
-
10 mM, 40-100% inhibition
monoiodoacetate
-
-
additional information
-
L-monapterin does not inhibit activity
-
additional information
P27213
NaCl 100 mM and KCl 100 mM have no effect on activity
-
additional information
G3FNL7, -
not inhibitory: dithiothreitol
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
dithioerythritol
P27213
increased catalytic activity with 10 mM
dithioerythritol
-
increased catalytic activity with 10 mM
dithioerythritol
-
increased catalytic activity with 10 mM
EDTA
-
1-5 mM, 110-120% activation
additional information
-
NADPH is not necessary for activity
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.8
-
6-(L-erythro-1,2-dihydroxypropyl 3-monophosphate)-7,8-dihydropterin
-
pH 7.4, 37C
0.0022
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
-
0.0055
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
S19A mutant enzyme
0.008
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
wild-type enzyme
0.008
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
pH 7.4, 37C
0.0081
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
wild-type enzyme
0.0091
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
P27213
-
0.01
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
-
0.011
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
wild-type enzyme
0.012
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
Q03393
-
0.013
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
mutant enzyme P87L
0.0305
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
mutant enzyme R25Q
0.0308
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
mutant enzyme R16C
0.1
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
-
5
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
mutant enzyme E133Q
17.7
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
mutant enzyme H89N
0.0005
-
7,8-dihydroneopterin triphosphate
-
mutant E133Q pH 7.4, 37C
0.00177
-
7,8-dihydroneopterin triphosphate
-
mutant H89N pH 7.4, 37C
0.0022
-
7,8-dihydroneopterin triphosphate
-
pH 7.4, 37C
0.008
-
7,8-dihydroneopterin triphosphate
-
pH 7.4, 37C
0.0085
-
7,8-dihydroneopterin triphosphate
-
pH 7.4, 37C
0.0091
-
7,8-dihydroneopterin triphosphate
P27213
pH 7.4, 37C
0.01
-
7,8-dihydroneopterin triphosphate
-
pH 7.4, 37C, shows positive cooperativity
0.01
-
7,8-dihydroneopterin triphosphate
-
pH 7.5, 37C
0.011
-
7,8-dihydroneopterin triphosphate
-
pH 7.4, 37C
0.0124
-
7,8-dihydroneopterin triphosphate
Q03393
90 KDa protein pH 7.4, 37C
0.0128
-
7,8-dihydroneopterin triphosphate
-
pH 8.5, 37C, 1 mM Mg2+
0.0169
-
7,8-dihydroneopterin triphosphate
-
pH 8.5 37C, 5 mM Mg2+
0.1
-
7,8-dihydroneopterin triphosphate
-
pH 7.5, 37C
0.164
-
7,8-dihydroneopterin triphosphate
G3FNL7, -
pH 7.5, 25C
0.92
-
sepiapterin
-
pH 7.5, 37C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.01
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
mutant enzyme P87L
0.012
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
mutant enzyme R16C
0.02
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
mutant enzyme R25Q
0.032
-
6-(L-erythro-1,2-dihydroxypropyl 3-triphosphate)-7,8-dihydropterin
-
wild-type enzyme
additional information
-
dihydroneopterin triphosphate
-
0.080 mU/min/mg
additional information
-
dihydroneopterin triphosphate
-
0.277 mU/min/mg
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00023
-
-
SSCR activity
0.00034
-
-
SSCR activity
0.00039
-
-
PTPS activity
0.000611
-
-
during the third trimester, enzyme assays at 37C and pH 7.4
0.000714
-
-
during the first trimester, enzyme assays at 37C and pH 7.4
0.000782
-
-
during the second trimester, enzyme assays at 37C and pH 7.4
0.00113
-
-
PTPS activity
0.00891
-
-
PTPS activity
0.01303
-
-
PTPS activity
0.0253
0.0255
-
pH 7.4, 37C, no differences observed in the enzyme activity between pregnant and non-pregnant women
0.044
-
-
R16C mutant enzyme
0.0574
-
-
-
0.074
-
-
R25Q mutant enzyme
0.077
-
-
-
0.09767
-
-
SSCR activity
0.09936
-
-
SSCR activity
0.1
-
-
-
0.12
-
-
-
0.12
-
-
wild-type enzyme
0.129
-
-
S19A mutant enzyme
0.2766
-
-
-
0.2883
-
P27213
-
0.5167
-
Q03393
-
4.6
-
-
-
40
-
-
-
57.4
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
in cells treated with mixed inflammatory cytokines IFNgamma, TNFalpha and IL-1, PTPS messenger RNA abundance and enzyme activity are 10fold and 3fold higher than in untreated cells, respectively
additional information
-
-
0.3 microU/mg protein
additional information
-
-
10fold more Flag-tag fused PTPS per total protein in cytoplasm compared to nucleus, no activity of Flag-tag fused PTPS in the nucleus; 18 microU/mg total protein
additional information
-
-
1.4 mU/mg in brain determined with the ONPG-assay with the o-nitrophenyl-beta-D-glactopyranoside substrate of a mouse heterozygous for the Pts-lacZ allele (encoding a fusion protein of N-terminal 35 amino acids of 6-pyruvoyl-tetrahydropterin synthase and beta-galactosidase), 1 U is defined as 1 OD at 420 nm per minute at pH 7.5 and 37C; 2.2 mU/mg in liver determined with the ONPG-assay with the o-nitrophenyl-beta-D-glactopyranoside substrate of a mouse heterozygous for the Pts-lacZ allele (encoding a fusion protein of N-terminal 35 amino acids of 6-pyruvoyl-tetrahydropterin synthase and beta-galactosidase), 1 U is defined as 1 OD at 420 nm per minute at pH 7.5 and 37C; 3.5 mU/mg in liver determined with the ONPG-assay with the o-nitrophenyl-beta-D-glactopyranoside substrate of a mouse homozygous for the Pts-lacZ allele (encoding a fusion protein of N-terminal 35 amino acids of 6-pyruvoyl-tetrahydropterin synthase and beta-galactosidase), 1 U is defined as 1 OD at 420 nm per minute at pH 7.5 and 37C
additional information
-
-
5.3 pmol/min/10*10 platelets, PTPS activity does not change significantly after treatment with glucocorticoids in a dose equivalent to at least 100 mg prednisone for at least 7 days, enzyme assays at 37C
additional information
-
-
no enzymatic activity detected
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
7
P27213
-
7
-
G3FNL7, -
-
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
P27213
assay at
7.5
8
Q03393
-
7.5
-
-
; in Tris-HCl 100 mM
7.5
-
-
; in Tris-HCl 100 mM
7.5
-
-
; in Tris-HCl 100 mM
7.5
-
-
assay at
8.5
-
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
10
G3FNL7, -
-
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
37
-
-
assay at
37
-
P27213
assay at
37
-
-
assay at
37
-
G3FNL7, -
-
60
80
-
3.2fold increase in activity compared to that at 37C
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
-
G3FNL7, -
70% of maximum activity
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
partial purification
Manually annotated by BRENDA team
-
in brain nuclear beta-galactosidase expression in neurons located in prominent catecholaminergic cell groups such as substantia nigra and locus coeruleus, in the ventral part of the hypothalamus, in the hippocampus and in the amygdala. nuclear and cytoplasmic beta-galactosidase expression in germinal periventricular layer
Manually annotated by BRENDA team
-
the starting cells, which are harvested just after plating on the developmental plate exhibit high PTPS mRNA. After 4 h, the transcripts decrease dramatically and then remain at the levels thereafter, although increases slightly at the terminal stage (after 12 h)
Manually annotated by BRENDA team
-
the starting cells, which are harvested just after plating on the developmental plate exhibit high PTPS mRNA. After 4 h, the transcripts decrease dramatically and then remain at the levels thereafter, although increases slightly at the terminal stage (after 12 h)
-
Manually annotated by BRENDA team
-
tissue from normal pregnant women
Manually annotated by BRENDA team
-
monkey kidney cells, CRL 1650
Manually annotated by BRENDA team
-
cells from patients with BH4 deficiency
Manually annotated by BRENDA team
-
in kidney very weak beta-galactosidase expression in adult and strong expression in newborn mice heterozygous for the Pts-lacZ allele (encoding a fusion protein of N-terminal 35 amino acids of 6-pyruvoyl-tetrahydropterin synthase and beta-galactosidase). Localization in the cytoplasm but not in the nucleus in all cells lining the proximal convoluted tube in adult and newborn mice. No staining in the medulla of newborn mice. Nuclear localization in the thin limb of the Henle loops in adult mice
Manually annotated by BRENDA team
-
fat bodies
Manually annotated by BRENDA team
-
high homology with rat protein but different amine terminus
Manually annotated by BRENDA team
Q03393
acute lymphoblastic leukemia cell line, 65% homology with rat enzyme
Manually annotated by BRENDA team
-
heat instability, it is present in the anterior pituitary endothelial cells but not in posterior pituitary
Manually annotated by BRENDA team
-
neuroblastoma cells, CRL 2271
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
immunofluorescence, Western blot analysis
Manually annotated by BRENDA team
-
weak staining in immunohistochemistry
Manually annotated by BRENDA team
-
immunofluorescence, Western blot analysis
Manually annotated by BRENDA team
-
strong staining in immunohistochemistry
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Plasmodium falciparum (isolate 3D7)
Plasmodium vivax (strain Salvador I)
Plasmodium vivax (strain Salvador I)
Plasmodium vivax (strain Salvador I)
Plasmodium vivax (strain Salvador I)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
68000
-
-
gel filtration
68000
-
-
gel filtration
72000
-
-
native PAGE
83000
-
-
gel filtration
83000
-
-
-
83000
-
P27213
HPLC gel filtration
83000
-
-
gel filtration, seems to have 4 identical subunits
83000
-
-
gel filtration of active enzyme seems to have larger molecular mass forms
85000
87000
-
gel filtration
90000
-
Q03393
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 15855, calculation from nucleotide sequence
?
-
x * 16500, SDS-PAGE
?
Q03393
x * 17000, SDS-PAGE
?
-
x * 16000, SDS-PAGE and electrospray ionization-mass spectometry
?
-
x * 16199, mutant protein R16C, electrospray mass spectrometry; x * 16224, mutant protein R25Q, electrospray mass spectrometry
?
P27213
x * 17000, SDS-PAGE
?
-
x * 19000, SDS-PAGE
?
-
x * 16000, SDS-PAGE; x * 17000, SDS-PAGE
?
-
x * 37500, SDS-PAGE
?
G3FNL7, -
* 21000, SDS-PAGE
dimer
-
2 * or 1 * 16255, wild-type enzyme occurs as monomeric or dimeric form, electrospray mass spectrometry
dimer
-
2 * 37500, also evidence for higher multimeric forms, SDS-PAGE
hexamer
-
6 * 16254, electron-ionization mass spectrometry; 6 * 97000, SDS-PAGE
pentamer
-
5 * 16000, SDS-PAGE; 5 * 16257, electrospray ionization-mass spectrometry
tetramer
-
4 * 16500, SDS-PAGE
tetramer
-
-
tetramer
-
4 * 17208, electrospray ionization mass spectrometry
tetramer
Q03393
4 * 17000, SDS-PAGE
tetramer
-
4 * 18500, SDS-PAGE
tetramer
P27213
4 * 17000, SDS-PAGE
tetramer
-
4 * 19000, SDS-PAGE
trimer
-
3 * 47000, SDS-PAGE
trimer
-
3 * 15899, electron-ionization mass spectrometry
monomer
-
1 * or 2 * 16255, wild-type enzyme occurs as monomeric or dimeric form, electrospray mass spectrometry
additional information
-
each subunit consists of 144 residues with 2497 non-hydrogen atoms
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
no glycoprotein
-
no carbohydrates bound
glycoprotein
-
-
additional information
P27213
mature protein lacks 4 N-terminal amino acids residues
additional information
-
free of mannose and glucose residues
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ePTPS is crystallized using the hanging-drop vapour-diffusion method. Hexagonal- and rectangular shaped crystals are obtained. Diffraction data are collected from the hexagonal and rectangular crystals to 3.0 and 2.3 A resolution, respectively. The hexagonal plate-shaped crystals belonged to space group P321, with unit-cell parameters a = b = 112.59, c = 68.82 A , and contained two molecules in the asymmetric unit. The rectangular crystals belonged to space group I222, with unit-cell parameters a = 112.76, b = 117.66, c = 153.57 A, and contain six molecules in the asymmetric unit
-
X-ray crystallography
-
overexpressed as native and selenomethionine-substituted protein and the purified protein is crystallized by the oil-microbatch method at 22C. 2.1 A resolution from the native crystal using synchrotron radiation at 100 K. The crystal belongs to the orthorhombic space group P212121, with unit-cell parameters a = 35.83, b = 95.71, c = 05.65 A. The selenomethionine-substituted crystal is isomorphous to the native crystal and diffracts X-rays to 2.9 A
-
X-ray crystallography, sitting drop vapor diffusion
-
X-ray crystal structure of the PTPS homolog from Streptomyces coelicolor, SCO 6650, is solved at 1.5 A resolution. SCO 6650 forms a hexameric T-fold that closely resembles other PTPS proteins. The biological activity of SCO 6650 is unknown, but it lacks both a required active-site zinc metal ion and the essential catalytic triad and does not catalyze the PTPS reaction. SCO 6650 maintains active-site residues consistent with binding a pterin-like substrate
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
80
-
-
5 min, 25% loss of activity
80
-
-
24% retention of activity after 10 min
80
-
-
-
additional information
-
-
the human pituitary gland enzyme is heat instable in contrast to the enzyme from human, rat and salmon liver, and Drosophila heads
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
stable at all steps of purification
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, PIPES 50 mM, stable for 1 year
-
-70C, stable
-
-20C and -70C, Tris HCl, several months, stable
-
-70C, stable for several months
-
-70C, stable for at least 1 year
P27213
4C, Tris-HCl, 4 weeks, no degradation
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ammonium sulfate precipitation, hydroxyapatite column, gel filtration
-
SDS-PAGE
-
immobilized metal ion affinity chromatography (Ni2+)
-
ammonium sulfate precipitation, Affigel Blue chromatography, DEAE-Bio-gel chromatography, Affigel Blue chromatography, SDS-PAGE
-
extraction, chromatography on a column of Ni-NTA gel
-
using Ni-NTA chromatography
-
affinity chromatography, gel filtration
Q03393
affinity chromatography, gel filtration , SDS-PAGE
-
affinity chromatography, gel filtration, SDS-PAGE
-
ammonium sulfate precipitation, DEAE-Sephadex A50 column
-
ammonium sulfate precipitation, hydroxyapatite column, gel filtration, DEAE-Fractogel 650S column, SDS-PAGE
-
extraction, chromatography on an amylose resin column
-
immobilized metal ion affinity chromatography (Ni2+)
-
recombinant protein
G3FNL7, -
affinity chromatography, gel filtration, SDS-PAGE
-
ammonium sulfate precipitation, hydroxyapatite column, butyl-toyopearl chromatography, gel filtration, HPLC ion exchange column
P27213
ammonium sulfate precipitation, hydrofobic interaction chromatography, gel filtration, ion exchange, hydroxyapatite chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
His-tagged version expressed in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expressed in Escherichia coli BL21(DE3)
-
expression in Escherichia coli
-
cloned in Escherichia coli
Q03393
expressed as maltose-binding-6-pyruvoyl-tetrahydropterin-synthase fusion protein
-
expression in Cos-1 cells
-
expression in Escherichia coli
-
expression in Escherichia coli and COS-1 cells, wild-type enzyme and 4 naturally occurring mutants
-
His-tagged version expressed in Escherichia coli BL21(DE3)
-
expression in Escherichia coli
G3FNL7, -
expression in Escherichia coli
C6KTB6
cloned
P27213
cloned in Escherichia coli
-
cloned in Escherichia coli; expressed as maltose-binding-6-pyruvoyl-tetrahydropterin-synthase fusion protein
-
expressed in Escherichia coli as a His-tagged fusion protein
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C10A
-
50% decrease in activity
D96N
-
mutant enzyme that causes PTPS deficiency
Delta1-11
-
Flag-tag fused PTPS with N-terminal deletion, 97% decrease in activity
DELTA119-145
-
Flag-tag fused PTPS with C-terminal deletion, no detectable activity, no more nuclear staining
DELTA143-145
-
Flag-tag fused PTPS with C-terminal deletion, no detectable activity, no more nuclear staining
DELTAV57
-
mutant enzyme DELTAV57 is incorrectly folded and thus unstable
P87L
-
phosphorylated, 30% of activity of wild type enzyme
R16C
-
37% of activity of wild type enzyme. Forms stable homomultimers and exhibit significant activity in vitro, but no activity in COS-1 cells
R16C
-
89% decrease in activity
R25G
-
mutant enzyme that causes PTPS deficiency
R25Q
-
61% of activity of wild type enzyme. Phosphorylated, forms stable homomultimers and exhibit significant activity in vitro, but no activity in COS-1 cells
R25Q
-
96% decrease in activity
R87L
-
has substantial activity but enhanced sensitivity to local unfolding
T106M
-
mutant enzyme that causes PTPS deficiency
V56M
-
mutant enzyme that causes PTPS deficiency
V70D
-
mutant enzyme that causes PTPS deficiency
C42A
-
no catalytic activity, complete loss of metal binding site and activity, it is the only Cys in the active site
E133Q
-
1.3% of wild-type activity but similar affinity for the substrate
H23L
-
complete loss of metal binding site and activity
H48L
-
complete loss of metal binding site and activity
H50L
-
complete loss of metal binding site and activity
H89N
-
4.3% of wild-type activity but similar affinity for the substrate
K143A
-
35% decrease in activity
additional information
-
fusion protein of PTPS with a N-terminally fused Flag-tag set on 100% of activity, 55% decreased activity of fusion protein of PTPS with a C-terminally fused Flag-tag, 49% increase in activity of fusion protein consisting of PTPS and both N-terminally fused Flag-tag and a N-terminally fused nuclear localization signal
additional information
-
compound heterozygous or homozygous mutations are spread over the entire genes for PTS with 44 mutant alleles
additional information
-
Pts-/- mice rescued by a transgenic introduction of human PTS cDNA under the control of the human promoter of the dopamine beta-hydroxylase represent a mouse model for dopa-responsive dystonia. Mutant mice exhibit motor deficits and manifested a major depletion of tyrosine hydroxylase (TH) labeling in the striatum, with a marked posterior-to-anterior gradient resulting in near total loss caudally. Within the regions of remaining TH staining in the striatum, there is a greater loss of TH labeling in striosomes than in the surrounding matrix. The predominant loss of TH expression in striosomes occurrs during the early postnatal period, when motor symptoms first appear
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
the decrease of this enzyme is the most frequent cause of atypical phenylketonuria
medicine
-
lack of tetrahydrobiopterin leads to hyperphenylalaninemia and a deficiency of biogenic amine neurotransmitters such as dopamine and serotonin and severe progressive mental retardation