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Information on EC 3.5.4.16 - GTP cyclohydrolase I and Organism(s) Rattus norvegicus and UniProt Accession P22288
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3.5.4.16 GTP cyclohydrolase IIUBMB Comments
The reaction involves hydrolysis of two C-N bonds and isomerization of the pentose unit; the recyclization may be non-enzymic. 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 4.2.3.12 (6-pyruvoyltetrahydropterin synthase) .
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Word Map
- 3.5.4.16
- tetrahydrobiopterin
- bh4
- endothelial
- dystonia
- hydroxylase
-
dopa-responsive
- dopamine
- sepiapterin
- biopterin
- parkinsonism
- pterins
- pteridine
- catecholamine
- dihydrofolate
- serotonin
-
segawa
- interferon-gamma
-
neurotransmitter
- 2,4-diamino-6-hydroxypyrimidine
- folate
- levodopa
- l-dopa
- ptp
- dihydropteridine
-
dopaminergic
-
diurnal
-
nigrostriatal
-
endothelium-dependent
- striatum
- dahp
- phenylketonuria
- hyperphenylalaninemia
-
cytokine-stimulated
- nutrition
- dihydropteroate
-
ido
- n-acetylserotonin
-
6r-l-erythro-5,6,7,8-tetrahydrobiopterin
- 7,8-dihydrobiopterin
- 6-pyruvoyl-tetrahydropterin
- dihydrobiopterin
- molecular biology
- indoleamine
- tetrahydropterin
- biotechnology
- medicine
-
catecholaminergic
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
gtp cyclohydrolase i, gtpch, gtp cyclohydrolase, gtp cyclohydrolase 1, gtp-ch, gtp-cyclohydrolase i, gch-1, gtpch1, gtpch i, guanosine triphosphate cyclohydrolase i, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dihydroneopterin triphosphate synthase
-
-
-
-
GTP 8-formylhydrolase
-
-
-
-
GTP cyclohydrolase
-
-
-
-
guanosine triphosphate 8-deformylase
-
-
-
-
guanosine triphosphate cyclohydrolase
-
-
-
-
hydrolase, guanosine triphosphate cyclo-
-
-
-
-
Punch protein
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
allosteric regulation mechanism, active site structure
-
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
reaction and regulation mechanism, enzyme forms a stimulatory complex with the GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
amidine hydrolysis
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
GTP 7,8-8,9-dihydrolase
The reaction involves hydrolysis of two C-N bonds and isomerization of the pentose unit; the recyclization may be non-enzymic. 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 4.2.3.12 (6-pyruvoyltetrahydropterin synthase) [3].
CAS REGISTRY NUMBER
COMMENTARY
37289-19-3
-
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
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
rate-limiting step in the biosynthesis of tetrahydrobiopterin, a key factor necessary for nitric oxide synthase, and for the hydrolxylases that are involved in the production of catecholamines and serotonin
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
estrogens play a regulatory role on the enzyme expression, the enzyme is involved in estrogen receptor interaction with cyclic AMP, role of receptor subtypes, overview
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
the enzyme controls the biosynthesis pathway of tetrahydrobiopterin, which is a necessary cofactor for inducible nitric oxide synthase
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
the enzyme is feedback regulated by the GTPCH feedback regulatory protein GFRP, overview
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
-
first step in pathway of pterins
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
-
-
-
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
-
first step of the biosynthesis of (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, i.e. BH4
-
-
?
additional information
?
-
-
enzyme deficiency causes hyperphenylalaninemia with severe neurological disorders, the 3,4-dihydroxyphenylalanine, i.e. DOPA, responsive form of dystonia, and endothelial dysfunction, all by (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin depletion, the GTP cyclohydrolase I feedback regulatory protein GFRP binds to the enzyme and mediates the regulation of the enzyme by L-phenylalanine and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
-
?
additional information
?
-
-
tetrahydrobiopterin, the cofactor required for hydroxylation of aromatic amino acids, regulates its own synthesis through feedback inhibition of the enzyme mediated by the regulatory subunit called GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
-
-
?
additional information
?
-
-
enzyme is complexed with the GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP, in a ratio of 1:2, complex formation is induced by phenylalanine and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
-
?
additional information
?
-
-
enzyme is complexed with the GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP, in a ratio of 1:2, complex formation is induced by phenylalanine and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, i.e. BH4
-
-
?
additional information
?
-
-
GCH-1 interacts with many signal transduction proteins such as receptors (NKG2-A/B-actvating NK receptor and latrophilin-2), kinase (Death-associated protein kinase 3), adaptors (Rho-GTPase-activating protein 7 and Rho-guanine nucleotide exchange factor 3) and transcriptional factors (ATF-6 alpha and interferon regulatory factor 1)
-
-
?
additional information
?
-
-
GCH1 interacts with GCH1 interacts with GTP cyclohydrolase I feedback regulatory protein, GFRP, and very long-chain specific acyl-CoA dehydrogenase in the liver, tubulin beta-2A chain in the liver and brain, DnaJ homolog subfamily A member 1 and fatty aldehyde dehydrogenase in the liver, heart and kidney and eukaryotic translation initiation factor 3 subunit I in all organs tested, overview. GCH1 associates with mitochondrial proteins and interacts with VLCAD, a mitochondrial protein
-
-
?
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
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
-
first step of the biosynthesis of (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, i.e. BH4
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
rate-limiting step in the biosynthesis of tetrahydrobiopterin, a key factor necessary for nitric oxide synthase, and for the hydrolxylases that are involved in the production of catecholamines and serotonin
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
estrogens play a regulatory role on the enzyme expression, the enzyme is involved in estrogen receptor interaction with cyclic AMP, role of receptor subtypes, overview
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
the enzyme controls the biosynthesis pathway of tetrahydrobiopterin, which is a necessary cofactor for inducible nitric oxide synthase
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
the enzyme is feedback regulated by the GTPCH feedback regulatory protein GFRP, overview
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
-
first step in pathway of pterins
-
?
additional information
?
-
-
enzyme deficiency causes hyperphenylalaninemia with severe neurological disorders, the 3,4-dihydroxyphenylalanine, i.e. DOPA, responsive form of dystonia, and endothelial dysfunction, all by (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin depletion, the GTP cyclohydrolase I feedback regulatory protein GFRP binds to the enzyme and mediates the regulation of the enzyme by L-phenylalanine and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
-
?
additional information
?
-
-
tetrahydrobiopterin, the cofactor required for hydroxylation of aromatic amino acids, regulates its own synthesis through feedback inhibition of the enzyme mediated by the regulatory subunit called GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
-
-
?
additional information
?
-
-
GCH1 interacts with GCH1 interacts with GTP cyclohydrolase I feedback regulatory protein, GFRP, and very long-chain specific acyl-CoA dehydrogenase in the liver, tubulin beta-2A chain in the liver and brain, DnaJ homolog subfamily A member 1 and fatty aldehyde dehydrogenase in the liver, heart and kidney and eukaryotic translation initiation factor 3 subunit I in all organs tested, overview. GCH1 associates with mitochondrial proteins and interacts with VLCAD, a mitochondrial protein
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dihydrobiopterin
-
induction of feedback inhibition, binding site structure
GTP cyclohydrolase I feedback regulatory protein GFRP
-
natural inhibitor, inhibition mechanism, in vitro inhibition together with 2,4-diamino-6-hydroxypyrimidine, the inhibition is fully reversible by L-phenylalanine, regulatory function in physiological feedback inhibition, overview
-
GTPCH feedback regulatory protein
-
GFRP, the allosteric regulatory protein GFRP triggers a noncompetitive attenuation of GTPCH activity, an allosteric effector is unnecessary for GFRP to influence GTPCH activity. GFRP-mediated allosteric regulation by small molecule effectors is indistinguishable for truncated mutant DELTA45-GTPCH and wild-type GTPCH
-
streptozotocin
-
the expression of GCH-I is decreased by streptozotocin treatment (60 mg/kg iv, 7 weeks)
additional information
-
the N-terminal peptide of mammalian GTP cyclohydrolase I is an autoinhibitory control element and contributes to binding the allosteric regulatory protein GFRP. The autoinhibitory peptide provides a molecular mechanism for physiological up-regulation of GTPCH activity
-
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
i.e. BH4, feedback inhibition mediated by GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP, in complex with the enzyme, binding site structure
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
i.e. BH4, feedback inhibition mediated by GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP, inhibition is enhaced by dGTP
2,4-Diamino-6-hydroxypyrimidine
-
direct inhibitition at higher concentrations
2,4-Diamino-6-hydroxypyrimidine
-
DAHP, the inhibition mechanism involves the GTP cyclohydrolase I feedback regulatory protein GFRP, overview, the inhibition is fully reversible by L-phenylalanine
L-erythro-5,6,7,8-tetrahydrobiopterin
-
indirect inhibition of 2,4-diamino-6-hydroxypyrimidine at lower concentrations with the help of feedback regulatory protein
L-erythro-5,6,7,8-tetrahydrobiopterin
-
L-phenylalanine reverses inhibition
L-erythro-5,6,7,8-tetrahydrobiopterin
-
with help of feedback regulatory protein
tetrahydrobiopterin
-
induction of feedback inhibition of the enzyme via mediation of GFRP which forms a complex with the enzyme, binding site structure
tetrahydrobiopterin
-
the cofactor required for hydroxylation of aromatic amino acids regulates its own synthesis through feedback inhibition of the enzyme mediated by the regulatory subunit called GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
tetrahydrobiopterin
-
BH4, can limit its own synthesis by triggering decameric GTPCH to assemble in an inhibitory complex with two GTPCH feedback regulatory protein, GFRP, pentamers
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
17beta-estradiol
-
can regulate GTPCH gene expression via transcriptional mechanisms
L-phenylalanine
-
feed-forward stimulation at subsaturating concentration of GTP mediated by GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
L-phenylalanine
-
feed-forward stimulation at subsaturating concentration of GTP mediated by GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP, in complex with the enzyme, binding site structure
L-phenylalanine
-
stimulates the enzyme via mediation of GFRP which forms a complex with the enzyme
additional information
GTP-CH 1 mRNA and protein expression is unaltered by renal ischemia-reperfusion
-
additional information
-
GTP-CH 1 mRNA and protein expression is unaltered by renal ischemia-reperfusion
-
additional information
-
estrogen-triggered activation of GTP cyclohydrolase 1 gene expression, time course in transfected cells and mechanism, overview
-
additional information
-
lipopolysaccharide application by injection increases enzyme expression in kidney, but not in liver and lung
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin and Phe ligand binding kinetics of the enzyme complex at pH 6.0 and pH 7.2
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.8
additional information
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
multimeric assemblies of wild-type GTPCH and truncation mutant DELTA45-GTPCH on their own display markedly different banding patterns
metabolism
physiological function
metabolism
-
GCH-1 is the rate-limiting enzyme for tetrahydrobiopterin synthesis
metabolism
-
the N-terminal peptide of mammalian GTP cyclohydrolase I is an autoinhibitory control element and contributes to binding the allosteric regulatory protein GFRP
physiological function
-
GCH-1 is a key enzyme in de novo tetrahydrobiopterin biosynthesis. GCH-1 is critical for maintaining coupled NOS activity and aromatic amino acid hydroxylation, pain sensitivity and chronicity, and immune responses
physiological function
-
GCH1 might have broader functions beyond tetrahydrobiopterin biosynthesis. It interacts with proteins in an organ dependent manner and eukaryotic translation initiation factor 3 subunit I, EIF3I, might be a general regulator of GCH1. GCH1 is regulated by protein-protein interaction
physiological function
-
the autoinhibitory peptide provides a molecular mechanism for physiological up-regulation of GTPCH activity. GTPCH activity regulation by GTPCH feedback regulatory protein, GFRP
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). GCH1_RAT
241
0
27057
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decamer
additional information
decamer
-
2 pentamers which are positioned in a head-to-head manner to form the active decameric enzyme with an active site at the interface of each couple of dimer
additional information
-
stimulatory and inhibitory enzyme-GFRP-complex sandwich structure, subunit composition of GFRP pentamer is betabetaalphabetabetaalphabetabeta, overview
additional information
-
multimeric assemblies of wild-type GTPCH and truncation mutant DELTA45-GTPCH on their own display markedly different banding patterns
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
GCH-1 has 8 potential phosphorylation sites (Ser51, Ser72, Thr85, Thr91, Thr103, Ser130, Ser167, and Thr231). Overexpressed rat GCH-1 is phosphorylated at Ser51, Ser167, and Thr231 in HEK-293 cells
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
5 mg/ml enzyme subunit GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP, free and complexed with the human catalytic subunit of the enzyme, batch procedure, at 4°C overnight, total reflection X-ray fluorescence spectrometry, structure determination and analysis at 2.6 A resolution, modeling
-
crystallization of purified recombinant enzyme and protein GFRP forming a BH2-induced inhibitory complex, involving dGTP, in 14% isopropanol, 0.2 M ammonium sulfate, 10% PEG 300, 10% ethylene glycol, 0.1 M MES-Na, pH 6.0, rapid freezing of crystals in liquid nitrogen, X-ray diffraction structure determination and analysis at 2.8 A resolution
-
purified recombinant enzyme complexed with recombinant wild-type and selenomethionine derivatized GFRP, the complex with the latter being used as CH3HGCl derivative, 5 mg/ml protein complex in 24% v/v 2-methyl-2,4-pentanediol, 75 mM Tris-HCl, pH 7.5, 50 mM KCl, 5 mM phenylalanine, X-ray diffraction structure determination and analysis at 2.7-2.8 A resolution, model building
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S130A
-
phospho-defective mutant with significantly decreased GCH-1 activity
S72A
-
phospho-defective mutant with significantly decreased GCH-1 activity
T103A
-
phospho-defective mutant with significantly decreased GCH-1 activity
T231A
-
mutant with 23% increased GCH-1 activity but reduced GCH-1 nuclear localization and nuclear GCH-1 activity
T91A
-
phospho-defective mutant with significantly decreased GCH-1 activity
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
GCH1 in complexes with cellular proteins from organs liver, heart, brain, and kidney, by immunoaffinity chromatography, isolation of mitochondria from liver, heart and kidney
-
recombinant His-tagged wild-type GTPCH maltose-binding protein fusion protein from Escherichia coli by amylose affinity chromatography and cleavage of the fusion tag by TEV protease, purification of His-tagged DELTA45-GTPCH mutant from HEK-293 cells by metal affinity chromatography
-
recombinant maltose binding protein fusion enzyme fromn Escherichia coli strain DH5alpha
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of His-tagged wild-type GTPCH as maltose-binding protein fusion protein in Escherichia coli, expression of a His-tagged GTPCH truncation mutant, devoid of 45 N-terminal amino acids, DELTA45-GTPCH, in HEK-293 cells
-
expression of the enzyme in Escherichia coli strain DH5alpha as maltose binding protein fusion protein
-
transient co-expression of the enzyme with estrogen receptors in PC12 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
tetracycline stimulation substantially increases GCH-1 activity about 20fold
-
the autoinhibitory peptide provides a molecular mechanism for physiological up-regulation of GTPCH activity
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sawada, M.; Horikoshi, T.; Masada, M.; Akino, M.; Sugimoto, T.M.; Matsuura, S.; Nagatsu, T.
A sensitive assay of GTP cyclohydrolase I activity in rat and human tissues using radioimmunoassay of neopterin
Anal. Biochem.
154
361-366
1986
Homo sapiens, Rattus norvegicus
Blau, N.; Niederwieser, A.
GTP-cyclohydrolases: a review
J. Clin. Chem. Clin. Biochem.
23
169-176
1985
Geobacillus stearothermophilus, Comamonas sp., Escherichia coli, Lactiplantibacillus plantarum, Mammalia, Rattus norvegicus, Serratia indica
Blau, N.; Niederwieser, A.
GTP-cyclohydrolases: mini-review
Biochem. Clin. Aspects Pteridines
3
77-92
1984
Geobacillus stearothermophilus, Gallus gallus, Comamonas sp., Drosophila melanogaster, Escherichia coli, Lactiplantibacillus plantarum, Rattus norvegicus, Serratia indica
-
Hatakeyama, K.; Harada, T.; Kagamiyama, H.
IMP dehydrogenase inhibitors reduce intracellular tetrahydrobiopterin levels through reduction of intracellular GTP levels
J. Biol. Chem.
267
20734-20739
1992
Homo sapiens, Rattus norvegicus
Xie, L.; Smith, J.A.; Gross, S.S.
GTP cyclohydrolase I inhibition by the prototypic inhibitor 2,4-diamino-6-hydroxypyrimidine
J. Biol. Chem.
273
21091-21098
1998
Rattus norvegicus
Yoneyama, T.; Brewers, J.M.; Hatakeyama, K.
GTP cyclohydrolase I feedback regulatory protein is a pentamer of identical subunits
J. Biol. Chem.
272
9690-9696
1997
Rattus norvegicus
Milstien, S.; Jaffe, H.; Kowlessu, D.; Bonner, T.I.
Purification and cloning of the GTP cyclohydrolase I feedback regulatory protein, GFRP
J. Biol. Chem.
271
19743-19751
1996
Rattus norvegicus
Hattori, Y.; Gross, S.S.
GTP cyclohydrolase I mRNA is induced by LPS in vascular smooth muscle: Characterization, sequence and relationship to nitric oxide synthase
Biochem. Biophys. Res. Commun.
195
435-441
1993
Rattus norvegicus
Maita, N.; Hatakeyama, K.; Okada, K.; Hakoshima, T.
Structural basis of biopterin-induced inhibition of GTP cyclohydrolase I by GFRP, its feedback regulatory proteins
J. Biol. Chem.
279
51534-51540
2004
Rattus norvegicus
Bader, G.; Schiffmann, S.; Herrmann, A.; Fischer, M.; Gutlich, M.; Auerbach, G.; Ploom, T.; Bacher, A.; Huber, R.; Lemm, T.
Crystal structure of rat GTP cyclohydrolase I feedback regulatory protein, GFRP
J. Mol. Biol.
312
1051-1057
2001
Rattus norvegicus
Maita, N.; Okada, K.; Hatakeyama, K.; Hakoshima, T.
Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP
Proc. Natl. Acad. Sci. USA
99
1212-1217
2002
Rattus norvegicus
Yoneyama, T.; Hatakeyama, K.
Ligand binding to the inhibitory and stimulatory GTP cyclohydrolase I/GTP cyclohydrolase I feedback regulatory protein complexes
Protein Sci.
10
871-878
2001
Rattus norvegicus
Hung, Y.C.; Tsai, P.S.; Huang, C.J.; Yang, S.; Skimming, J.W.; Hsieh, M.C.
Change in expression of the guanosine triphosphate cyclohydrolase I in LPS-stimulated rats is tissue specific
Acta Anaesthesiol. Taiwan.
42
23-31
2004
Rattus norvegicus
Kolinsky, M.A.; Gross, S.S.
The mechanism of potent GTP cyclohydrolase I inhibition by 2,4-diamino-6-hydroxypyrimidine: requirement of the GTP cyclohydrolase I feedback regulatory protein
J. Biol. Chem.
279
40677-40682
2004
Rattus norvegicus
Serova, L.I.; Filipenko, M.; Schilt, N.; Veerasirikul, M.; Sabban, E.L.
Estrogen-triggered activation of GTP cyclohydrolase 1 gene expression: Role of estrogen receptor subtypes and interaction with cyclic AMP
Neuroscience
140
1253-1263
2006
Rattus norvegicus
Seujange, Y.; Eiam-Ong, S.; Tirawatnapong, T.; Eiam-Ong, S.
Role of angiotensin II on dihydrofolate reductase, GTP-cyclohydrolase 1 and nitric oxide synthase expressions in renal ischemia-reperfusion
Am. J. Nephrol.
28
692-700
2008
Rattus norvegicus (P22288), Rattus norvegicus
Wenzel, P.; Schulz, E.; Oelze, M.; Mueller, J.; Schuhmacher, S.; Alhamdani, M.S.; Debrezion, J.; Hortmann, M.; Reifenberg, K.; Fleming, I.; Muenzel, T.; Daiber, A.
AT1-receptor blockade by telmisartan upregulates GTP-cyclohydrolase I and protects eNOS in diabetic rats
Free Radic. Biol. Med.
45
619-626
2008
Rattus norvegicus
Du, J.; Wei, N.; Xu, H.; Ge, Y.; Vasquez-Vivar, J.; Guan, T.; Oldham, K.T.; Pritchard, K.A.; Shi, Y.
Identification and functional characterization of phosphorylation sites on GTP cyclohydrolase I
Arterioscler. Thromb. Vasc. Biol.
29
2161-2168
2009
Rattus norvegicus
Du, J.; Xu, H.; Wei, N.; Wakim, B.; Halligan, B.; Pritchard, K.A.; Shi, Y.
Identification of proteins interacting with GTP cyclohydrolase I
Biochem. Biophys. Res. Commun.
385
143-147
2009
Rattus norvegicus
Higgins, C.E.; Gross, S.S.
The N-terminal peptide of mammalian GTP cyclohydrolase I is an autoinhibitory control element and contributes to binding the allosteric regulatory protein GFRP
J. Biol. Chem.
286
11919-11928
2011
Rattus norvegicus
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Transporter Classification Database (TCDB): 9.B.10.1.1
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