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Information on EC 3.5.4.16 - GTP cyclohydrolase I and Organism(s) Drosophila melanogaster
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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
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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
-
catecholaminergic
The taxonomic range for the selected organisms is: Drosophila melanogaster
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
-
-
-
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GTP cyclohydrolase
-
-
-
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guanosine triphosphate 8-deformylase
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-
-
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guanosine triphosphate cyclohydrolase
-
-
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hydrolase, guanosine triphosphate cyclo-
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-
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Punch protein
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
amidine hydrolysis
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-
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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
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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
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
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-
-
-
?
additional information
?
-
-
GTP cyclohydrolase I stimulates tyrosine hydroxylase activity by increasing the maximal velocity of the enzyme and fails to block the feedback inhibition of tyrosine hydroxylase by dopamine
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-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
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-
-
?
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
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
GTP cyclohydrolase I stimulates tyrosine hydroxylase activity by increasing the maximal velocity of the enzyme and fails to block the feedback inhibition of tyrosine hydroxylase by dopamine
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-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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GTP cyclohydrolase I is activated by phosphorylation with protein kinase C or A
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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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
Dube3a, the fly UBE3A orthologue, positively regulates Punch/GCH1 in the fly brain. GCH1 is a UBE3A target involved in neurotransmitter regulation and has broad implications for how the function of this target may contribute to the pathogenesis of Angelman syndrome, duplication 15q autism as well as idiopathic autism linked to UBE3A regulated pathways
malfunction
three different heterozygous mutations in the Punch gene enhance the gmr-Dube3a rough eye phenotype causing a glazed appearance, loss of inter-ommatidial bristles and often displaying yellowish discoloration indicative of underlying neurodegeneration. In the heterozygous state these mutations in Punch show no eye phenotype when crossed to the gmr-GAL4 driver alone and the individual UAS-Dube3a stocks without gmr-GAL4 do not have rough eyes
malfunction
three different heterozygous mutations in the Punch gene enhance the gmr>Dube3a rough eye phenotype causing a glazed appearance, loss of inter-ommatidial bristles and often displaying yellowish discoloration indicative of underlying neurodegeneration. In the heterozygous state these mutations in Punch show no eye phenotype when crossed to the gmr-GAL4 driver alone and the individual UAS-Dube3a stocks without gmr-GAL4 do not have rough eyes
metabolism
the Punch protein, an enzyme that produces tetrahydrobiopterin, is the rate-limiting co-factor in monoamine synthesis. Dube3a, the fly UBE3A orthologue, regulates Punch/GCH1 in the fly brain. Drosophila Ube3a regulates monoamine synthesis by increasing GTP cyclohydrolase I activity via a non-ubiquitin ligase mechanism, overview
metabolism
the Punch protein, an enzyme that produces tetrahydrobiopterin, is the rate-limiting cofactor in monoamine synthesis. Dube3a, the fly UBE3A orthologue, regulates Punch/GCH1 in the fly brain. Drosophila Ube3a regulates monoamine synthesis by increasing GTP cyclohydrolase I activity via a non-ubiquitin ligase mechanism, overview
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_DROME
324
0
35541
Swiss-Prot
other Location (Reliability: 1)
D8FT24_DROME
181
0
20276
TrEMBL
other Location (Reliability: 5)
E4NKN2_DROME
308
0
33877
TrEMBL
other Location (Reliability: 1)
C6TP60_DROME
325
0
35419
TrEMBL
other Location (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
39000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S37E
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the enzymatic activity is significantly higher than of wild type GTPCH isoform C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, Ni-NTA column chromatography, and Sephacryl S-300HR gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Dube3a has a co-transcriptional activation function for GCH1
Dube3a has a co-transcriptional activation function for GCH1. Punch protein isoform B levels change as a result of Dube3a overexpression or loss of function in the fly brain
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
molecular biology
molecular biology
mutations in Punch can act as genetic enhancers of Dube3a over-expression phenotypes
molecular biology
mutations in Punch can act as genetic enhancers of Dube3a overexpression phenotypes
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Weisberg, E.P.; O'Donnell, J.M.
Purification and characterization of GTP cyclohydrolase I from Drosophila melanogaster
J. Biol. Chem.
261
1453-1458
1986
Drosophila melanogaster
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
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Funderburk, C.D.; Bowling, K.M.; Xu, D.; Huang, Z.; ODonnell, J.M.
A typical N-terminal extensions confer novel regulatory properties on GTP cyclohydrolase isoforms in Drosophila melanogaster
J. Biol. Chem.
281
33302-33312
2006
Drosophila melanogaster
Bowling, K.M.; Huang, Z.; Xu, D.; Ferdousy, F.; Funderburk, C.D.; Karnik, N.; Neckameyer, W.; O'Donnell, J.M.
Direct binding of GTP cyclohydrolase and tyrosine hydroxylase: regulatory interactions between key enzymes in dopamine biosynthesis
J. Biol. Chem.
283
31449-31459
2008
Drosophila melanogaster
Ferdousy, F.; Bodeen, W.; Summers, K.; Doherty, O.; Wright, O.; Elsisi, N.; Hilliard, G.; O'Donnell, J.M.; Reiter, L.T.
Drosophila Ube3a regulates monoamine synthesis by increasing GTP cyclohydrolase I activity via a non-ubiquitin ligase mechanism
Neurobiol. Dis.
41
669-677
2011
Drosophila melanogaster (D8FT24), Drosophila melanogaster (E4NKN2), Drosophila melanogaster (P48596)
EXTERNAL LINKS (specific for EC-Number 3.5.4.16)
Transporter Classification Database (TCDB): 9.B.10.1.1
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