3.5.4.16: GTP cyclohydrolase I
This is an abbreviated version!
For detailed information about GTP cyclohydrolase I, go to the full flat file.
Word Map on EC 3.5.4.16
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3.5.4.16
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tetrahydrobiopterin
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bh4
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endothelial
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dystonia
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hydroxylase
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dopa-responsive
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dopamine
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sepiapterin
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biopterin
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parkinsonism
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pterins
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pteridine
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catecholamine
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dihydrofolate
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serotonin
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segawa
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interferon-gamma
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neurotransmitter
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2,4-diamino-6-hydroxypyrimidine
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folate
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levodopa
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l-dopa
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ptp
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dihydropteridine
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dopaminergic
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diurnal
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nigrostriatal
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endothelium-dependent
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striatum
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dahp
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phenylketonuria
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hyperphenylalaninemia
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cytokine-stimulated
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nutrition
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dihydropteroate
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ido
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n-acetylserotonin
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6r-l-erythro-5,6,7,8-tetrahydrobiopterin
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7,8-dihydrobiopterin
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6-pyruvoyl-tetrahydropterin
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dihydrobiopterin
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molecular biology
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indoleamine
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tetrahydropterin
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biotechnology
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medicine
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catecholaminergic
- 3.5.4.16
- tetrahydrobiopterin
- bh4
- endothelial
- dystonia
- hydroxylase
-
dopa-responsive
- dopamine
- sepiapterin
- biopterin
- parkinsonism
- pterins
- pteridine
- catecholamine
- dihydrofolate
- serotonin
-
segawa
- interferon-gamma
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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
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6r-l-erythro-5,6,7,8-tetrahydrobiopterin
- 7,8-dihydrobiopterin
- 6-pyruvoyl-tetrahydropterin
- dihydrobiopterin
- molecular biology
- indoleamine
- tetrahydropterin
- biotechnology
- medicine
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catecholaminergic
Reaction
Synonyms
dihydroneopterin triphosphate synthase, FelE, folE, GCH, GCH-1, GCH1, GCHI, GCYH-IA, GCYH-IB, GTP 8-formylhydrolase, GTP CHase I, GTP cyclohydrolase, GTP cyclohydrolase 1, GTP cyclohydrolase I, GTP cyclohydrolase IA, GTP cyclohydrolase IB, GTP cyclohydrolase-1, GTP-CH, GTP-CH-I, GTP-CH1, GTP-cyclohydrolase 1, GTP-cyclohydrolase I, GTPCH, GTPCH I, GTPCH-1, GTPCH1, GTPCHI, guanosine 5'-triphosphate-cyclohydrolase I, guanosine triphosphate 8-deformylase, guanosine triphosphate cyclohydrolase, guanosine triphosphate cyclohydrolase 1, guanosine triphosphate cyclohydrolase I, guanosine-5'-triphosphate cyclohydrolase 1, hydrolase, guanosine triphosphate cyclo-, MptA, Punch, Punch protein
ECTree
3.5.4.16 GTP cyclohydrolase IAdvanced search results
results (
results (Inhibitors
Inhibitors on EC 3.5.4.16 - GTP cyclohydrolase I
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
dihydrobiopterin
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induction of feedback inhibition, binding site structure
GTP cyclohydrolase feedback regulatory protein
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i.e. GFRP, GTP cyclohydrolase I, GTPCH-1, undergoes negative feedback regulation by its endproduct tetrahydrobiopterin via interaction with the GTP cyclohydrolase feedback regulatory protein, GFRP. GFRP binding increased the apparent Km of GTPCH-1, which also contributes to inhibition and increases the cooperativity of substrate binding in the wild-type but not the S81D mutant. GFRP both inhibits and stimulates GTPCH-1 activity in vitro depending on interactions with either tetrahydrobiopterin or phenylalanine. GTPCH-1 phosphorylation reduces its binding to GFRP
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GTP cyclohydrolase I feedback regulatory protein GFRP
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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
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GTPCH feedback regulatory protein
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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
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H2O2
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more than 0.3 mM H2O2 result in a decrease in activity of GTPCHI, the function of the GTP cyclohydrolase I/GTP cyclohydrolase I feedback regulatory protein complex is not affected by H2O2
streptozotocin
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the expression of GCH-I is decreased by streptozotocin treatment (60 mg/kg iv, 7 weeks)
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
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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
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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
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direct inhibitition at higher concentrations
2,4-Diamino-6-hydroxypyrimidine
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DAHP, the inhibition mechanism involves the GTP cyclohydrolase I feedback regulatory protein GFRP, overview, the inhibition is fully reversible by L-phenylalanine
8-oxo-GTP
competitive inhibitor. The inhibitor interacts with a conserved active site Cys149, and this residue is S-nitrosylated. Ki/Km: 0.022
8-oxo-GTP
competitive inhibition, binds tightly to the enzyme with higher affinity than GTP, structure and binding network, overview
Co2+
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inhibition by elimination of the required metal-free GTP when present at high concentration with respect to the GTP concentration, overview
L-erythro-5,6,7,8-tetrahydrobiopterin
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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
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L-phenylalanine reverses inhibition; with help of feedback regulatory protein
Mg2+
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inhibition by elimination of the required metal-free GTP when present at high concentration with respect to the GTP concentration, formation of Mg-GTP, overview
Mn2+
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inhibition by elimination of the required metal-free GTP when present at high concentration with respect to the GTP concentration, overview
tetrahydrobiopterin
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GTP cyclohydrolase I, GTPCH-1, undergoes negative feedback regulation by its endproduct tetrahydrobiopterin via interaction with the GTP cyclohydrolase feedback regulatory protein, GFRP
tetrahydrobiopterin
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induction of feedback inhibition of the enzyme via mediation of GFRP which forms a complex with the enzyme, binding site structure
tetrahydrobiopterin
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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
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BH4, can limit its own synthesis by triggering decameric GTPCH to assemble in an inhibitory complex with two GTPCH feedback regulatory protein, GFRP, pentamers
Zn2+
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inhibition by elimination of the required metal-free GTP when present at high concentration with respect to the GTP concentration, overview
additional information
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synthesis and inhibitory potential of 7-deazaguanine derivatives on GTPCH I, inhibitory mechanism, overview
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additional information
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Mn2+ enzyme is not inactivated by exposure to oxygen
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additional information
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GTP-CH1 activity can be inhibited by tetrahydrobiopterin through its protein-protein interactions with GTP-CH1 regulatory protein
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additional information
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asymmetric dimethylarginine, ADMA, decreases GCH1 protein, but not mRNA concentrations, in pulmonary arterial endothelial cells because of the ubiquitination and proteasome-dependent degradation of GCH1. Overexpression of CHIP potentiates, whereas a CHIP U-box domain mutant attenuates, ADMA-induced GCH1 degradation and reductions in cellular BH4 concentrations. L-Arginine acts antagonistic and restores the activities
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additional information
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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
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