Information on EC 3.5.4.16 - GTP cyclohydrolase I

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

EC NUMBER
COMMENTARY
3.5.4.16
-
RECOMMENDED NAME
GeneOntology No.
GTP cyclohydrolase I
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
; the reaction involves hydrolysis of two C-N bonds and isomerization of the pentose unit, the recyclization may be non-enzymatic
-
-
-
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
reaction mechanism, six consecutive unimolecular reaction steps, the first of which being reversible
-
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
allosteric regulation mechanism, active site structure
-
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
reaction mechanism involving reaction intermediates
-
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
reaction mechanism, active site structure, GTP binding strcuture
P0A6T5
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
enzyme contains to thiol groups per active site, reaction mechanism
-
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
The reaction involves hydrolysis of two C-N bonds and isomerization of the pentose unit, the recyclization may be non-enzymic, reaction mechanism
-
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
reaction and regulation mechanism, enzyme forms a stimulatory complex with the GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
-
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
substrate binding and reaction mechanism, transition state structure, modelling, overview
Q5SH52, -
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
amidine hydrolysis
-
-
-
-
C-N bond cleavage
-
-
PATHWAY
KEGG Link
MetaCyc Link
6-hydroxymethyl-dihydropterin diphosphate biosynthesis I
-
drosopterin and aurodrosopterin biosynthesis
-
Folate biosynthesis
-
Metabolic pathways
-
preQ0 biosynthesis
-
tetrahydrobiopterin biosynthesis I
-
tetrahydrobiopterin biosynthesis II
-
tetrahydrobiopterin biosynthesis III
-
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].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dihydroneopterin triphosphate synthase
-
-
-
-
GCH
Q05915
-
GCH
Q8GLS8
-
GCH
Nocardia sp. NRRL 5646
Q8GLS8
-
-
GCH1
D8FT24, E4NKN2, P48596
-
GCH1
Q05915
-
GCHI
Q05915
-
GCYH-IA
-
isozyme
GCYH-IB
-
isozyme
GCYH-IB
Q5F9K6
isozyme
GTP 8-formylhydrolase
-
-
-
-
GTP CHase I
-
-
GTP cyclohydrolase
-
-
-
-
GTP cyclohydrolase 1
-
-
GTP cyclohydrolase 1
-
-
GTP cyclohydrolase 1
-
-
GTP cyclohydrolase I
Q8S3C2
-
GTP cyclohydrolase I
-
-
GTP cyclohydrolase I
-
-
GTP cyclohydrolase I
-
-
GTP cyclohydrolase I
-
-
GTP cyclohydrolase I
Q8VYU3
-
GTP cyclohydrolase IA
-
isozyme
GTP cyclohydrolase IB
-
isozyme
GTP cyclohydrolase IB
Q5F9K6
isozyme
GTP cyclohydrolase-1
-
-
GTP-CH
-
-
GTP-CH-I
-
-
GTP-CH-I
P30793
-
GTP-CH1
-
-
GTP-CH1
-
-
GTP-cyclohydrolase 1
-
-
GTP-cyclohydrolase 1
-
-
GTP-cyclohydrolase I
-
-
GTP-cyclohydrolase I
-
-
GTP-cyclohydrolase I
-
-
GTPCH
Mus musculus C57BL6
-
-
-
GTPCH I
-
-
GTPCH I
-
-
GTPCH-1
-
-
GTPCHI
-
-
GTPCHI
Methanocaldococcus jannaschii MJ0775
-
-
-
GTPCHI
-
-
guanosine 5'-triphosphate-cyclohydrolase I
-
-
guanosine triphosphate 8-deformylase
-
-
-
-
guanosine triphosphate cyclohydrolase
-
-
-
-
guanosine triphosphate cyclohydrolase 1
-
-
guanosine triphosphate cyclohydrolase I
-
-
guanosine triphosphate cyclohydrolase I
-
-
guanosine triphosphate cyclohydrolase I
-
-
guanosine-5'-triphosphate cyclohydrolase 1
-
-
hydrolase, guanosine triphosphate cyclo-
-
-
-
-
MptA
Methanocaldococcus jannaschii MJ0775
-
-
-
Punch
D8FT24, E4NKN2, P48596
-
Punch protein
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
37289-19-3
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
isozyme Pu-RA; GTP cyclohydrolase isoform Pu-RA
UniProt
Manually annotated by BRENDA team
isozyme Pu-RB; GTP cyclohydrolase isoform Pu-RB
UniProt
Manually annotated by BRENDA team
isozyme Pu-RC; GTP cyclohydrolase isoform Pu-RC
UniProt
Manually annotated by BRENDA team
IMR-32 neuroblastoma cells
-
-
Manually annotated by BRENDA team
alpha1, alpha and beta
-
-
Manually annotated by BRENDA team
Methanocaldococcus jannaschii MJ0775
strain MJ0775
-
-
Manually annotated by BRENDA team
precursor
SwissProt
Manually annotated by BRENDA team
precursor; C3H/HeN and C3H/HeJ mice
SwissProt
Manually annotated by BRENDA team
strain C57BL/6
-
-
Manually annotated by BRENDA team
Mus musculus C57BL6
-
-
-
Manually annotated by BRENDA team
strain NRRL 5646
SwissProt
Manually annotated by BRENDA team
Nocardia sp. NRRL 5646
strain NRRL 5646
SwissProt
Manually annotated by BRENDA team
lambs
-
-
Manually annotated by BRENDA team
swallowtail butterfly
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
PC-12 pheochromocytoma cells
-
-
Manually annotated by BRENDA team
Serratia indica
-
-
-
Manually annotated by BRENDA team
Serratia indica
multiple forms, D-I, D-II
-
-
Manually annotated by BRENDA team
strain HB8
Uniprot
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
decreases in GTPCH activity and expression in late stages of acute cardiac rejection due to a deficit in BH4. Mechanism of the decreased rejection appears related to decreased T cell proliferation and modulation of immune function by higher expression of genes involved in hematopoietic/stromal cell development and recruitment
malfunction
-
decreases in GTPCH activity and expression in late stages of acute cardiac rejection due to a deficit in BH4
malfunction
-
multimeric assemblies of wild-type GTPCH and truncation mutant DELTA45-GTPCH on their own display markedly different banding patterns
malfunction
D8FT24, E4NKN2, P48596
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; 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
Mus musculus C57BL6
-
decreases in GTPCH activity and expression in late stages of acute cardiac rejection due to a deficit in BH4
-
metabolism
-
GTPCH I is the rate-limiting enzyme for de novo tetrahydrobiopterin synthesis
metabolism
-
GTP cyclohydrolase I is the rate-limiting enzyme in generation of tetrahydrobiopterin
metabolism
-
GCH-1 is the rate-limiting enzyme for tetrahydrobiopterin synthesis
metabolism
-
GTP cyclohydrolase I is the rate-limiting enzyme for tetrahydrobiopterin synthesis
metabolism
-
GCH1 is the rate-limiting enzyme in the generation of BH4
metabolism
-
GTP cyclohydrolase I, GTPCH-1, is the rate-limiting enzyme involved in de novo biosynthesis of tetrahydrobiopterin, an essential cofactor for nitric oxide synthases and aromatic amino acid hydroxylases
metabolism
-
the N-terminal peptide of mammalian GTP cyclohydrolase I is an autoinhibitory control element and contributes to binding the allosteric regulatory protein GFRP
metabolism
D8FT24, E4NKN2, P48596
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; 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; 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
physiological function
-
endothelium-specific GTP cyclohydrolase I overexpression accelerates refractory wound healing in streptozotocin-induced type 1 diabetic mice through enhanced constitutive NOS activity and suppressed oxidative stress
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
-
isozyme GCYH-IB functions to allow folate biosynthesis during Zn2+ starvation, isozyme GCYH-IB functionally replaces GCYH-IA in Bacillus subtilis under zinc-limiting conditions
physiological function
Q5F9K6
isozyme GCYH-IB functions to allow folate biosynthesis during Zn2+ starvation
physiological function
-
GTP cyclohydrolase I is the rate-limiting enzyme for tetrahydrobiopterin synthesis. Cardiac myocyte-specific overexpression of human GTP cyclohydrolase I protects against acute cardiac allograft rejection
physiological function
-
GTP cyclohydrolase I interaction is required for degradation of the C-terminus of heat shock protein 70-interacting protein. GCH1 is a client protein for Hsp90. The U-box domain of CHIP is essential for ADMA-mediated GCH1 degradation in pulmonary arterial endothelial cells
physiological function
-
GTP cyclohydrolase I, GTPCH-1, is the rate-limiting enzyme involved in de novo biosynthesis of tetrahydrobiopterin, an essential cofactor for nitric oxide synthases and aromatic amino acid hydroxylases. GTPCH-1 undergoes negative feedback regulation by its endproduct tetrahydrobiopterin via interaction with the GTP cyclohydrolase feedback regulatory protein, GFRP. GTPCH-1 levels, GTPCH-1 phosphorylation status and GFRP levels play critical roles in regulating eNOS uncoupling in response to oscillatory shear stress, overview
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
physiological function
D8FT24, E4NKN2, P48596
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; 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; 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
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
Mus musculus C57BL6
-
GTP cyclohydrolase I is the rate-limiting enzyme for tetrahydrobiopterin synthesis. Cardiac myocyte-specific overexpression of human GTP cyclohydrolase I protects against acute cardiac allograft rejection
-
metabolism
Mus musculus C57BL6
-
GTP cyclohydrolase I is the rate-limiting enzyme for tetrahydrobiopterin synthesis
-
additional information
-
adult cardiac myocytes despite expression of GTPCH mRNA and protein have a defective basal and cytokine-stimulated synthesis of BH4 via the de novo synthesis pathway and impaired synthesis via the salvage pathway in contrast with that typically seen in neonatal cardiac myocytes
additional information
-
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. Hsp90-GCH1 interactions are reduced, whereas the association of GCH1 with Hsp70 and the C-terminus of Hsp70-interacting protein, i.e. CHIP, increases in the cells. In vivo Hsp90/GCH1 interactions are decreased, whereas GCH1-Hsp70 and GCH1-CHIP interactions and GCH1 ubiquitination are increased. L-Arginine acts antagonistic and restores the activities
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone triphosphate + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
P0A6T5
substrate is the reaction intermediate of the overall reaction
-
-
?
beta,gamma-methyleneguanosine 5'-triphosphate + H2O
dihydroneopterin 2',3'-cyclic phosphate + ?
show the reaction diagram
Methanocaldococcus jannaschii, Methanocaldococcus jannaschii MJ0775
-
-
-
-
?
beta-gamma-methyleneguanosine 5'-triphosphate + H2O
beta-gamma-methylene-7,8-dihydroneopterin 3'-triphosphate + formate
show the reaction diagram
-
-
-
?
GDP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine diphosphate
show the reaction diagram
Q5SH52, -
-
i.e. dihydroneopterin 3'-triphosphate
-
?
GDP + H2O
dihydroneopterin 2',3'-cyclic phosphate + ?
show the reaction diagram
Methanocaldococcus jannaschii, Methanocaldococcus jannaschii MJ0775
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q5SH52, -
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
P0A6T5
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
P22288
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Serratia indica
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Serratia indica
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Serratia indica
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Serratia indica
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
P30793
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q8S3C2
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q8VYU3
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q05915
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q5F9K6
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q5SH52, -
-
i.e. dihydroneopterin 3'-triphosphate
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q8GLS8
first committed step in the biosynthesis of tetrahydrofolate and tetrahydrobiopterin
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin, important in the regulation of monoamine neurotransmitters such a s dopamine, norepinephrine, and serotonin
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
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
show the reaction diagram
Q8GLS8
complex series of reaction steps
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
P0A6T5
cyclization to dihydroneopterin triphosphate
i.e. dihydroneopterin triphosphate
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
substrate needs to be Mg2+-free
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q8VYU3
the enzyme mediates the first and committing step of the pterin branch of the folate-synthesis pathway
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q8S3C2
the enzyme mediates the first and committing step pf the pterin branch of the folate-synthesis pathway, the enzyme mediates the first and committing step of the pterin branch of the folate-synthesis pathway
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
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
show the reaction diagram
-
first step in the biosynthesis pathway leading to dihydrofolate and tetrahydrobiopterin
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
Q05915
the enzyme is rate limiting in the tetrahydrobiopterin biosynthesis in adipose tissue, overview
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
the enzyme produces the cofactor tetrahydrobiopterin essential for activities of tyrosine hydroxylase and DOPA decarboxylase
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
the enzyme synthesizes the cofactor for the reaction of the phenylalanine hydroxylase
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Nocardia sp. NRRL 5646
Q8GLS8
first committed step in the biosynthesis of tetrahydrofolate and tetrahydrobiopterin, complex series of reaction steps
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in biosynthesis of tetrahydrobiopterin, BH4
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
Serratia indica
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
Serratia indica
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
Serratia indica
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
Methanocaldococcus jannaschii MJ0775
-
-
-
-
?
GTP + H2O
dihydroneopterin triphosphate + formate
show the reaction diagram
-
-
-
-
?
GTP + H2O
dihydroneopterin triphosphate + formate
show the reaction diagram
-
-
-
-
?
GTP + H2O
dihydroneopterin triphosphate + formate
show the reaction diagram
-
first step in the biosynthesis of pteridine coenzymes, such as folic acid and tetrahydrobiopterin
-
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
show the reaction diagram
-
first commited step in the biosynthesis of tetrahydrofolate and tetrahydrobiopterin
-
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
show the reaction diagram
-
first step of the biosynthesis of (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, i.e. BH4
-
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
show the reaction diagram
-
enzyme catalyzed opening of the imidazole ring of GTP, kinetically competent reaction intermediate is 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone
-
-
?
GTP + H2O
2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone + ?
show the reaction diagram
-
mutant H179N is not able to perform the whole reaction step
-
-
r
GTP + H2O
formate + 7,8-dihydro-D-neopterin 2',3'-cyclic phosphate + diphosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
-
-
-
-
?
guanosine 5'-[gamma-thio]triphosphate + H2O
dihydroneopterin 2',3'-cyclic phosphate + ?
show the reaction diagram
-
-
-
-
?
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
?
-
-
isozyme GTPCHIa activity is involved in formation of the black markings on the larva during fourth ecdysis, pigmentation pathway overview
-
-
-
additional information
?
-
-
catalyzes the first step in the biosynthesis of methanopterin, no activity towards dGTP, ATP, GMP, ITP, fapy-GTP, or 7-methyl-GTP
-
-
-
additional information
?
-
-
GCYH-I is not only the first enzyme of the tetrahydrofolate and tetrahydropterin pathways, but also the first enzyme of queuosine and archaeosine biosynthesis
-
-
-
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
-
-
-
additional information
?
-
-
GTPCH I is the rate-limiting enzyme for de novo tetrahydrobiopterin synthesis
-
-
-
additional information
?
-
-
GTPCH1 via tetrahydrobiopterin maintains normal blood pressure and endothelial function in vivo by preserving nitric oxide synthesis by endothelial NO synthase
-
-
-
additional information
?
-
-
tetrahydrobiopterin production by GTPCH I occurs in close proximity to endothelial nitric oxide synthase
-
-
-
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
-
-
-
additional information
?
-
Methanocaldococcus jannaschii MJ0775
-
catalyzes the first step in the biosynthesis of methanopterin, no activity towards dGTP, ATP, GMP, ITP, fapy-GTP, or 7-methyl-GTP
-
-
-
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
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q5SH52, -
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
P0A6T5
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q8GLS8
first committed step in the biosynthesis of tetrahydrofolate and tetrahydrobiopterin
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin, important in the regulation of monoamine neurotransmitters such a s dopamine, norepinephrine, and serotonin
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
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
show the reaction diagram
Q8VYU3
the enzyme mediates the first and committing step of the pterin branch of the folate-synthesis pathway
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
Q8S3C2
the enzyme mediates the first and committing step pf the pterin branch of the folate-synthesis pathway, the enzyme mediates the first and committing step of the pterin branch of the folate-synthesis pathway
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
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
show the reaction diagram
-
first step in the biosynthesis pathway leading to dihydrofolate and tetrahydrobiopterin
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
Q05915
the enzyme is rate limiting in the tetrahydrobiopterin biosynthesis in adipose tissue, overview
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
the enzyme produces the cofactor tetrahydrobiopterin essential for activities of tyrosine hydroxylase and DOPA decarboxylase
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
-
the enzyme synthesizes the cofactor for the reaction of the phenylalanine hydroxylase
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in biosynthesis of tetrahydrobiopterin, BH4
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
Serratia indica
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
Serratia indica
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
Serratia indica
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
-
first step in pathway of pterins
-
?
GTP + H2O
dihydroneopterin triphosphate + formate
show the reaction diagram
-
-
-
-
?
GTP + H2O
dihydroneopterin triphosphate + formate
show the reaction diagram
-
first step in the biosynthesis of pteridine coenzymes, such as folic acid and tetrahydrobiopterin
-
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
show the reaction diagram
-
first commited step in the biosynthesis of tetrahydrofolate and tetrahydrobiopterin
-
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
show the reaction diagram
-
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
show the reaction diagram
Nocardia sp. NRRL 5646
Q8GLS8
first committed step in the biosynthesis of tetrahydrofolate and tetrahydrobiopterin
-
-
?
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
?
-
-
isozyme GTPCHIa activity is involved in formation of the black markings on the larva during fourth ecdysis, pigmentation pathway overview
-
-
-
additional information
?
-
-
catalyzes the first step in the biosynthesis of methanopterin
-
-
-
additional information
?
-
-
GCYH-I is not only the first enzyme of the tetrahydrofolate and tetrahydropterin pathways, but also the first enzyme of queuosine and archaeosine biosynthesis
-
-
-
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
-
-
-
additional information
?
-
-
GTPCH I is the rate-limiting enzyme for de novo tetrahydrobiopterin synthesis
-
-
-
additional information
?
-
-
GTPCH1 via tetrahydrobiopterin maintains normal blood pressure and endothelial function in vivo by preserving nitric oxide synthesis by endothelial NO synthase
-
-
-
additional information
?
-
-
tetrahydrobiopterin production by GTPCH I occurs in close proximity to endothelial nitric oxide synthase
-
-
-
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
-
-
-
additional information
?
-
Methanocaldococcus jannaschii MJ0775
-
catalyzes the first step in the biosynthesis of methanopterin
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Fe2+
-
dependent, contains 1 Fe2+ per protomer
K+
Serratia indica
-
activates
K+
-
activates
Li+
Serratia indica
-
activates
Mg2+
-
activates
Mn2+
-
at 2 mM Mn2+ is able to restore MptA activity to a higher level than Fe2+, Mn2+ enzyme is not inactivated by exposure to oxygen
Mn2+
-
required for activity of isozyme GCYH-1B
Na+
Serratia indica
-
activates
Zn2+
-
catalytically essential ion, complexed to 2 cysteine and 1 histidine residue
Zn2+
-
absolutely required, e.g. for activity and reconstitution of the denatured enzyme, 1 Zn2+ bound per subunit of the decameric enzyme
Zn2+
-
1 ion per active site
Zn2+
P0A6T5
required, wild-type enzyme contains 0.9 mol of Zn2+ per mol of enzyme subunit, while the zinc content of the mutant enzymes is reduced to below 0.2 Zn2+ per mol of enzyme subunit
Zn2+
-
essential for activity, coordinated to a His-side chain of the active site
Zn2+
-
essential for activity, coordinated to a His-side chain of the active site, mechanistic role
Zn2+
-
essential, bound to 2 Cys and 1 His
Zn2+
Q5SH52, -
the zinc ion is bound by residues Cys108, His111, and Cys179
Zn2+
-
isozyme GCYH-1A is a Zn2+-dependent enzyme, isozyme GCYH-IB is expressed only under Zn2+-limiting conditions
Mn2+
Q5F9K6
required for activity of isozyme GCYH-1B
additional information
-
no metals required
additional information
-
no metals required
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(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
2,4-Diamino-6-hydroxypyrimidine
-
-
7-methyl-GTP
-
36% inhibition at 2 mM GMP
8-Aminoguanosine triphosphate
-
-
8-Azaguanine
-
43% inhibition at 2.9 mM
8-ethoxycarbonyl-7-deazaguanine
-
78% inhibition at 2.9 mM
8-methyl-7-deazaguanine
-
94% inhibition at 2.9 mM
8-oxo-dGTP
Q5SH52, -
competitive inhibition
8-oxo-GTP
Q5SH52, -
competitive inhibition, binds tightly to the enzyme with higher affinity than GTP, structure and binding network, overview
8-trifluoromethyl-7-deazaguanine
-
17% inhibition at 2.9 mM
ADP
-
competitive inhibitor
Al3+
Serratia indica
-
-
ATP
-
competitive inhibitor
ATP
Serratia indica
-
-
ATP
Q5SH52, -
competitive inhibition
Ca2+
-
no activity detected regardless of metal concentration
caveolin-1
-
overexpression of caveolin-1 inhibits GTPCH I activity
-
Cd2+
Serratia indica
-
-
Cd2+
-
no activity detected regardless of metal concentration
Co2+
-
inhibition by elimination of the required metal-free GTP when present at high concentration with respect to the GTP concentration, overview
Co2+
-
24% residual activity at 0.1 mM
Co3+
-
no activity detected regardless of metal concentration
Cu2+
Serratia indica
-
-
Cu2+
-
no activity detected regardless of metal concentration
DAHP
-
non-competitive inhibitor
dGTP
-
competitive inhibitor
dGTP
Q5SH52, -
competitive inhibition
dGTP
-
28% inhibition at 2 mM GMP
dihydrobiopterin
-
induction of feedback inhibition, binding site structure
Divalent cations
-
-
-
EDTA
-
no activity of GCYH-IB is observed in the presence of EDTA
fapy-GMP
-
1 mM results in a 5fold reduction in activity
Fe2+
-
75% residual activity at 1 mM
-
Fe3+
Serratia indica
-
-
-
Fe3+
-
no activity detected regardless of metal concentration
-
GDP
Serratia indica
-
-
GMP
-
43% inhibition at 2 mM GMP
GTP
-
substrate inhibition above 0.2 mM
GTP
-
substrate inhibition above 0.2 mM
GTP
Q8VYU3
substrate inhibition above 0.1 mM
GTP cyclohydrolase feedback regulatory protein
-
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
-
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
-
guanosine 5'-tetraphosphate
-
-
H2O2
-
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
Hg2+
Serratia indica
-
-
L-erythro-5,6,7,8-tetrahydrobiopterin
-
-
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; with help of feedback regulatory protein
L-erythro-5,6,7,8-tetrahydrobiopterin
-
UTP reduces inhibition
L-erythro-7,8-dihydrobiopterin
-
-
L-Sepiapterin
-
-
Mg2+
-
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
Mg2+
-
43% residual activity at 0.1 mM
N-acetyl-serotonin
-
-
Ni2+
-
9.8% residual activity at 0.1 mM
p-chloromercuribenzoate
Serratia indica
-
-
PO43-
-
uncompetitive inhibitor
SO42-
Serratia indica
-
-
streptozotocin
-
the expression of GCH-I is decreased by streptozotocin treatment (60 mg/kg iv, 7 weeks)
tetrahydrobiopterin
-
feedback inhibition
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
-
-
tetrahydrobiopterin
-
GTP cyclohydrolase I, GTPCH-1, undergoes negative feedback regulation by its endproduct tetrahydrobiopterin via interaction with the GTP cyclohydrolase feedback regulatory protein, 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
TTP
-
competitive inhibitor
UTP
-
competitive inhibitor
Zn2+
Serratia indica
-
-
Zn2+
-
inhibition by elimination of the required metal-free GTP when present at high concentration with respect to the GTP concentration, overview
Zn2+
-
14% residual activity at 0.05 mM
Mn2+
-
inhibition by elimination of the required metal-free GTP when present at high concentration with respect to the GTP concentration, overview
additional information
-
no inhibition by EGTA
-
additional information
-
synthesis and inhibitory potential of 7-deazaguanine derivatives on GTPCH I, inhibitory mechanism, overview
-
additional information
-
Mn2+ enzyme is not inactivated by exposure to oxygen
-
additional information
-
GTP-CH1 activity can be inhibited by tetrahydrobiopterin through its protein-protein interactions with GTP-CH1 regulatory protein
-
additional information
-
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
-
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
17beta-estradiol
-
can regulate GTPCH gene expression via transcriptional mechanisms
H2O2
-
0.1 mM H2O2 is the optimum concentration for the activation of GTPCHI
interferon-gamma
-
GCH1 expression is strongly induced by a mixture of interleukin-1beta, tissue necrosis factor-alpha, and interferon-gamma released by microglia under brain-damaging conditions
-
Interleukin-1beta
-
GCH1 expression is strongly induced by a mixture of interleukin-1beta, tissue necrosis factor-alpha, and interferon-gamma released by microglia under brain-damaging conditions
-
L-phenylalanine
-
stimulates the enzyme via mediation of GFRP which forms a complex with the enzyme
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
-
feed-forward stimulation at subsaturating concentration of GTP mediated by GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
L-phenylalanine
-
feedback regulation via L-phenylalanine
tissue necrosis factor-alpha
-
GCH1 expression is strongly induced by a mixture of interleukin-1beta, tissue necrosis factor-alpha, and interferon-gamma released by microglia under brain-damaging conditions
-
lipolysaccharide
Q05915
commercially isolated from Escherichia coli serotype 026:B6, activates and upregulates the enzyme in adipose tissue, but in cultured 3T3-L1 adipocytes lipolysaccharide addition only increases the enzyme expression level in presence of TNFalpha and interferon gamma, overview
-
additional information
-
lipopolysaccharide application by injection increases enzyme expression in kidney, but not in liver and lung
-
additional information
-
estrogen-triggered activation of GTP cyclohydrolase 1 gene expression, time course in transfected cells and mechanism, overview
-
additional information
P22288
GTP-CH 1 mRNA and protein expression is unaltered by renal ischemia-reperfusion
-
additional information
-
GTP cyclohydrolase I is activated by phosphorylation with protein kinase C or A
-
additional information
-
GTPCH expression is regulated by inflammatory stimuli, in association with reduced expression of GTP cyclohydrolase feedback regulatory protein
-
additional information
-
reduction in GTP-CH1 regulatory protein expression following proinflammatory stimulation is necessary for optimal GTP-CH1 activity
-
additional information
-
S81 phosphorylation enhances GTPCH-1 enzyme activity
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0143
-
GDP
Q5SH52, -
pH 8.5, 25C, recombinant enzyme
0.0042
-
GTP
Q5SH52, -
pH 8.5, 25C, recombinant enzyme
0.007
-
GTP
Q8GLS8
recombinant enzyme expressed in Escherichia coli
0.00987
-
GTP
-
isozyme GCYH-IB, in 100 mM HEPES (pH 8.0), 100 mM KCl, 0.5 mM MnCl2, 1 mM dithiothreitol, temperature not specified in the publication
0.0173
-
GTP
-
-
0.0179
-
GTP
-
pH 7.8, 37C, wild-type enzyme
0.031
-
GTP
-
-
0.046
-
GTP
Q8VYU3
pH 8.0, 37C, recombinant enzyme
0.075
-
GTP
-
pH 7.8, 37C, recombinant enzyme
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
Serratia indica
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
stopped-flow kinetic analysis of the reaction, single turnover experiments, the rate-limiting step occurs rather late in the reaction sequence
-
additional information
-
additional information
-
association and dissociation constants of wild-type and mutant enzymes in oligomerization
-
additional information
-
additional information
-
kinetics of the reaction steps, single turnover experiments, wild-type and H179N mutant enzymes, overview
-
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
-
additional information
-
additional information
Q5SH52, -
steady-state kinetics
-
additional information
-
additional information
-
kinetics
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0017
-
GDP
Q5SH52, -
pH 8.5, 25C, recombinant enzyme
0.0011
-
GTP
-
isozyme GCYH-IB, in 100 mM HEPES (pH 8.0), 100 mM KCl, 0.5 mM MnCl2, 1 mM dithiothreitol, temperature not specified in the publication
0.0035
-
GTP
Q5SH52, -
pH 8.5, 25C, recombinant enzyme
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00022
-
8-oxo-dGTP
Q5SH52, -
pH 8.5, 25C, recombinant enzyme
0.0000054
-
8-oxo-GTP
Q5SH52, -
pH 8.5, 25C, recombinant enzyme
0.071
-
ATP
Q5SH52, -
pH 8.5, 25C, recombinant enzyme
0.02
-
dGTP
Q5SH52, -
pH 8.5, 25C, recombinant enzyme
0.173
-
GTP
Q8VYU3
pH 8.0, 37C, recombinant enzyme
additional information
-
additional information
Q5SH52, -
inhibition kinetics
-
additional information
-
additional information
-
inhibition kinetics
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.000001
-
Q8GLS8
wild-type native enzyme and recombinant HAT10-tagged enzyme from expression in Escherichia coli BL21(DE3)
0.000029
-
Q8GLS8
recombinant enzyme from expression in Mycobacterium smegmatis/pSMT-260
0.00027
-
Q8GLS8
recombinant HAT-tagged enzyme from expression in Escherichia coli JM109
0.00088
-
Q8GLS8
recombinant HAT-217-tagged enzyme from expression in Escherichia coli BL21(DE3)
0.088
-
P0A6T5
wild-type enzyme, substrate 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone triphosphate
0.091
-
P0A6T5
wild-type enzyme, substrate GTP
6
-
Q8GLS8
purified recombinant HAT-tagged enzyme expressed in Escherichia coli
67
-
Serratia indica
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
Serratia indica
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
reconstituted chimeric mutant dimers, overview
additional information
-
Q8GLS8
activity of differently expressed recombinant enzymes
additional information
-
Q05915
tissue dependent enzyme activity and effects of cytokines
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
8.5
-
mutant V150E
7
-
-
mutant S135C
7.3
-
-
phosphate buffer: 2 optima, pH 7.3 and 8.0
7.5
-
-
assay at
7.5
-
-
mutant H112D
7.5
-
-
assay at
7.6
-
-
-
7.8
-
-
assay at
8
8.5
-
-
8
-
-
phosphate buffer: 2 optima, pH 7.3 and 8.0
8
-
-
mutants H113N and R139C
8.5
-
-
assay at
8.5
-
-
wild-type enzyme and mutants R56L, C110G, E111K, L134Q, K136E, H179Q, C181S, and R185G
8.5
-
-
assay at
8.5
-
Q5SH52, -
assay at
8.5
-
-
assay at
8.6
-
Serratia indica
-
-
9
-
-
mutant E152K
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
Q5SH52, -
assay at
26
-
-
assay at
30
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
Q8GLS8
assay at
37
-
-
assay at
45
-
-
mutant E152K
55
-
-
mutants S135C and R185G
60
-
-
-
60
-
-
wild-type enzyme and mutant R139C
65
-
-
mutants H112D, K136E, and H179Q
70
-
-
mutant H113 N
72
-
-
mutant R56L
75
-
-
mutants C110G and L134Q
85
-
-
mutants E111K and V150E
90
-
-
mutant C181S
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
38
78
-
half-maximal activity at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Q05915
adipocyte cell line
Manually annotated by BRENDA team
D8FT24, E4NKN2, P48596
-
Manually annotated by BRENDA team
Mus musculus C57BL6
-
-
-
Manually annotated by BRENDA team
-
of pulmonary arteries, veins, airway epithelium, and nerves
Manually annotated by BRENDA team
-
larval, expression pattern of GTPCH isozymes Ia and Ib, overview
Manually annotated by BRENDA team
Q8VYU3
GCHI mRNA level is highest in unripe fruit
Manually annotated by BRENDA team
Mus musculus C57BL6
-
-
-
Manually annotated by BRENDA team
-
the black markings on the larva during fourth ecdysis are involving the GTPCHI activity
Manually annotated by BRENDA team
-
pulmonary arteries, veins, airway epithelium, and nerves, developmental regulation of GTP-CH1, equally expressed in pulmonary hypertensive and healthy piglets
Manually annotated by BRENDA team
-
aortic vascular, smooth
Manually annotated by BRENDA team
-
transfected with a tet-off plasmid and a plasmid encoding human GCH1, the stable clone is named tet-GCH cell
Manually annotated by BRENDA team
additional information
Q05915
GCH expression patterns
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
GTPCH I is also co-localized with caveolin-1 to caveolar membrane microdomains of endothelial cells
Manually annotated by BRENDA team
-
GTPCH I staining is localized to perinuclear regions of the cell
Manually annotated by BRENDA team
Mus musculus C57BL6
-
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Bacillus cereus (strain ATCC 14579 / DSM 31)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Neisseria gonorrhoeae (strain ATCC 700825 / FA 1090)
Neisseria gonorrhoeae (strain ATCC 700825 / FA 1090)
Nitrosomonas europaea (strain ATCC 19718 / NBRC 14298)
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Yersinia pseudotuberculosis serotype I (strain IP32953)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30000
-
-
SDS-PAGE
30000
-
-
SDS-PAGE
39000
-
-
isoform A, SDS-PAGE
45000
-
-
isoform B, SDS-PAGE
47000
-
-
isoform C, SDS-PAGE
50000
-
-
dimeric mutants K136E and R139C, gel filtration
50000
-
-
GFRP
84000
-
-
gel filtration
91000
-
Q8VYU3
gel filtration
105000
-
-
gel filtration
108600
-
Q5F9K6
isozyme GCYH-1B, apparent molecular weight estimated from gel filtration
120000
-
-
wild-type enzyme in presence of 0.3 M KCl, mutants C110G, E111K, H112D, and C181S, gel filtration
135000
-
-
gel filtration
170000
-
Serratia indica
-
gel filtration
200000
-
Serratia indica
-
gel filtration, D-I, D-II
210000
-
-
gel filtration
230000
-
-
gel filtration
250000
-
-
decameric wild-type enzyme, gel filtration
260000
-
-
GTP cyclohydrolase I
300000
-
-
larger than 300000, gel filtration
362000
-
-
gel filtration
400000
-
-
low molecular weight form, gel filtration
575000
-
-
gel filtration
600000
-
-
high molecular weight form, gel filtration
additional information
-
-
MW of mutant E152K is very high in gel filtration approximately corresponding to a didecameric form
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 30000, SDS-PAGE
decamer
-
10 * 25000, about, composed of a pentamers of 5 dimers, the active site is located at the interface between dimers, Lys136, Arg139, and Glu152 are especially important for the oligomerization
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
decamer
-
each subunit contains 1 active site
decamer
Q8GLS8
10 * 24563, sequence calculation, 10 * 24500, MALDI-TOF mass spectrometry, 10 * 35000, recombinant HAT-tagged enzyme
decamer
-
GTP cyclohydrolase I
decamer
Nocardia sp. NRRL 5646
-
10 * 24563, sequence calculation, 10 * 24500, MALDI-TOF mass spectrometry, 10 * 35000, recombinant HAT-tagged enzyme
-
dimer
Q8VYU3
2 * 50000
homodecamer
-
isozyme GCYH-1A
homodimer
-
2 * 37000, SDS-PAGE
homodimer
Methanocaldococcus jannaschii MJ0775
-
2 * 37000, SDS-PAGE
-
homotetramer
-
isozyme GCYH-1B
octamer
Serratia indica
-
8 * 25000, SDS-PAGE
pentamer
-
GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
polymer
-
x * 39000, SDS-PAGE
tetramer
-
4 * 51000, SDS-PAGE
tetramer
-
4 * 35000, SDS-PAGE
tetramer
-
4 * 58000, SDS-PAGE
homotetramer
Q5F9K6
4 * 28568, isozyme GCYH-1B, apparent molecular weight estimated from gel filtration
additional information
-
6-8 * 55700, SDS-PAGE
additional information
-
x * 41000, SDS-PAGE
additional information
-
stimulatory and inhibitory enzyme-GFRP-complex sandwich structure, subunit composition of GFRP pentamer is betabetaalphabetabetaalphabetabeta, overview
additional information
Q8GLS8
digestion of recombinant HAT-tagged enzyme with enterokinase results in proteins of 29.5 and 32.5 kDa
additional information
-
multimeric assemblies of wild-type GTPCH and truncation mutant DELTA45-GTPCH on their own display markedly different banding patterns
additional information
Nocardia sp. NRRL 5646
-
digestion of recombinant HAT-tagged enzyme with enterokinase results in proteins of 29.5 and 32.5 kDa
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
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
phosphoprotein
-
S81 phosphorylation enhances GTPCH-1 enzyme activity, GFRP modulates phosphorylation of GTPCH-1, and GTPCH-1 phosphorylation reduces its binding to GFRP, overview
additional information
-
ubiquitination and proteasome-dependent degradation of GCH1. The CHIP-ubiquitin pathway modifies GCH1 in a lamb model of pulmonary hypertension secondary to increased pulmonary blood flow
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
selenomethionine-labeled isozyme GCYH-IB, sitting drop vapor diffusion method, using polyethylene glycol 6000 (10-16% (w/v)), LiCl (1-1.4 M), Tris (50 mM, pH 9.0), and Tris-HCl (50 mM, pH 7.0)
-
crystallization of purified recombinant enzyme mutants H112S, H113S, and C181S, free, mutant H112S in 0.1 M MES, pH 6.0, 0.2 M sodium acetate, 3 mM sodium azide, or complexed with substrate GTP, mutants H112S and C181S in 0.1 M MOPS, pH 7.0, 10% w/v PEG 6000, 0.1 M ammonium sulfate, or mutant H113S in 0.1 M Tris-HCl, pH 8.5, 0.2 M (NH4)H2PO4, 50% v/v 2-methyl-2,4-pentanediol, addition of GTP for the complex formation, hanging drop vapour diffusion method at room temperature, X-ray diffraction structure determination and analysis at about 2.1-3.2 A resolution, modeling
P0A6T5
4.6 mg/ml purified recombinant DELTA42-hGTP-CH-I in 0.1 M potassium phosphate, pH 7.0, 0.02% NaN3, mixed with precipitation solution containing 6% PEG 6000, 150 mM KCl, 100 mM MOPS, pH 7.0, equilibration against precipitant solution, X-ray diffraction strcuture determination and analysis at 3.1 A resolution, modeling
-
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 4C 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
-
purified enzyme complexed with 8-oxo-GTP or 8-oxo-dGTP, and as free enzyme, hanging drop vapour diffusion method, 20C, 0.002 ml of 13.7 mg/ml protein is mixed with 0.002 ml reservoir solution containing 0.1 M HEPES, pH 6.8, 2.0 M ammonium sulfate, 3.4% PEG 400, and 15% glycerol, X-ray diffraction structure determination and analysis at 2.0 and 1.8 A or at 2.2. A resolution, respectively
Q5SH52, -
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8.4
-
-
stability maximum
additional information
-
-
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
no significant loss of activity after 5 h
50
-
-
88% of activity after 10 min
70
100
-
relative to a sample of the enzyme heated at 70C for 10 min, MptA lost 27% activity when it is incubated or 10 min at 80C, 60% activity at 90C, and 89% activity at 100C
80
-
-
human liver enzyme, half-life: 2 min
82
-
-
half-life: 7 min
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
bovine serum albumin stabilizes
-
ORGANIC SOLVENT
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dithiothreitol
-
in the absence of dithiothreitol, MptA loses all activity within 4 days at -20C, this activity can be restored by adding specific divalent metal ions to the oxygen-inactivated enzyme under anaerobic conditions in the presence of dithiothreitol
dithiothreitol
Methanocaldococcus jannaschii MJ0775
-
in the absence of dithiothreitol, MptA loses all activity within 4 days at -20C, this activity can be restored by adding specific divalent metal ions to the oxygen-inactivated enzyme under anaerobic conditions in the presence of dithiothreitol
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, 6 months, stable
-
4C, extreme instability of purified enzyme
-
-80C, 6 months, stable
-
-80C, 1 year, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ammonium sulfate precipitation, Ni-NTA column chromatography, and Sephacryl S-300HR gel filtration
-
Ni-NTA resin column chromatography
-
recombinant wild-type and mutant enzymes
-
expression of wild-type and mutant proteins in Escherichia coli
-
recombinant DELTA42-hGTP-CH-I from Escherichia coli M15
-
two forms
-
Mono Q HR column chromatography
-
recombinant HAT-tagged enzyme from Escherichia coli, 6.8fold
Q8GLS8
expression in Escherichia coli
-
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
-
-
Serratia indica
-
recombinant enzyme from Escherichia coli strain BL21(DE3) by ion exchange chromatography
Q5SH52, -
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
cloned into the yeast expression vector pVT103-U and introduced into yeast strain 971/6a
Q8S3C2
expressed in Escherichia coli B834(DE3) cells
-
expressed in Escherichia coli BL21(DE3)pLysS cells
-
overexpression of wild-type and mutant enzymes from plasmids in strain DH5alpha
-
expressed in Escherichia coli BL21 cells
-
expressed in Escherichia coli, baby hamster kidney cells, and NIH-293 cells
-
expressed in Mus musculus
-
expressed in Mus musculus microvascular endothelial cells
-
expression in Escherichia coli
-
expression of DELTA42-hGTP-CH-I in Escherichia coli M15
-
expression of GTPCH under the control of a 935-bp fragment of the mouse myosin heavy chain gene promoter
-
expressed in Escherichia coli strain BL21-Codon Plus (DE3)-PIL
-
expression of the enzyme in transgenic Lycopersicon esculentum plants using the Agrobacterium tumefaciens transfection system
Q05915
gene gch and adjacent regions, DNA and amino acid sequence determination and analysis, uncommon start codon TTG, ribosomal binding site, overexpression in Escherichia coli strains JM109 and BL21(DE3) as HAT-tagged enzyme, and expression in Mycobacterium smegmatis from plasmid
Q8GLS8
expressed in HEK-293 cells
-
expressed in PC-12 cells; transient co-expression of the enzyme with estrogen receptors in PC12 cells
-
expression in Escherichia coli
-
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
-
cloned into the yeast expression vector pVT103-U and introduced into yeast strain 971/6a
Q8VYU3
enzyme expression in Escherichia coli strain BL21(DE3)
Q5SH52, -
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Dube3a has a co-transcriptional activation function for GCH1; 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
D8FT24, E4NKN2, P48596
exposure to the NO donor spermine NONOate (0-0.1 mM) leads to an dose-dependent increase in GCH1 protein. GCH1 promoter activity is enhanced by spermine NONOate in a CREB-dependent manner
-
tetracycline stimulation substantially increases GCH-1 activity about 20fold
-
the autoinhibitory peptide provides a molecular mechanism for physiological up-regulation of GTPCH activity
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
S37E
-
the enzymatic activity is significantly higher than of wild type GTPCH isoform C
C110G
-
site-directed mutagenesis, 0.22% activity compared to the wild-type enzyme, increased temperature optimum
C110S
P0A6T5
highly reduced activity in both reaction steps using GTP or 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone triphosphate as substrate, reduced zinc content compared to the wild-type enzyme
C181S
-
site-directed mutagenesis, 0.29% activity compared to the wild-type enzyme, highly increased temperature optimum
C181S
P0A6T5
determination of crystal structure, highly reduced activity in both reaction steps using GTP or 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone triphosphate as substrate, reduced zinc content compared to the wild-type enzyme
E111K
-
site-directed mutagenesis, 3.1% activity compared to the wild-type enzyme, increased temperature optimum
E152K
-
site-directed mutagenesis, 0.06% activity compared to the wild-type enzyme, increased pH optimum, decreased temperature optimum
H112D
-
site-directed mutagenesis, 0.23% activity compared to the wild-type enzyme, decreased pH optimum, increased temperature optimum
H112S
P0A6T5
determination of crystal structure, highly reduced activity in both reaction steps using GTP or 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone triphosphate as substrate, reduced zinc content compared to the wild-type enzyme
H113N
-
site-directed mutagenesis, 67% activity compared to the wild-type enzyme, decreased pH optimum, increased temperature optimum
H113S
P0A6T5
determination of crystal structure, highly reduced activity in both reaction steps using GTP or 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone triphosphate as substrate, reduced zinc content compared to the wild-type enzyme
H179N
-
mutant H179N is not able to perform the whole reaction step, but can catalyzes the reversible formation of reaction intermediate 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone
H179Q
-
site-directed mutagenesis, 0.8% activity compared to the wild-type enzyme, increased temperature optimum
K136E
-
site-directed mutagenesis, 0.25% activity compared to the wild-type enzyme, increased temperature optimum
L134Q
-
site-directed mutagenesis, 1.85% activity compared to the wild-type enzyme, increased temperature optimum
R139C
-
site-directed mutagenesis, 29.3% activity compared to the wild-type enzyme, decreased pH optimum
R185G
-
site-directed mutagenesis, 2.9% activity compared to the wild-type enzyme, decreased temperature optimum
R56L
-
site-directed mutagenesis, 14% activity compared to the wild-type enzyme, increased temperature optimum
S135C
-
site-directed mutagenesis, 0.7% activity compared to the wild-type enzyme, decreased pH and temperature optimum
V150E
-
site-directed mutagenesis, 3.2% activity compared to the wild-type enzyme, slightly decreased pH optimum, increased temperature optimum
C265T
-
mutation results in the loss of the 177 C-terminal amino acids
G155S
-
the mutation is associated with Dopa-responsive dystonia in Chines Han population
G201E
-
no activity at 0.1 mM GTP
G201E
-
expression of the GCH mutant G201E (or the splicing variant GCH-II) causes intracellular inclusion bodies
R184H
-
very low activity at 0.1 mM GTP
R88W
-
very low activity at 0.1 mM GTP
S81A
-
site-directed mutagenesis, the mutant shows enhanced interaction with GFRP both in the presence of BH4 and GTP compared to the wild-type enzyme
S81D
-
site-directed mutagenesis, phospho-mimetic mutant that shows increased enzyme activity, reduced binding to GFRP, and resistance to inhibition by GFRP compared to wild-type GTPCH-1
H101N
-
shows wild type activity
H200N
-
shows reduced enzymatic activity but no reduction in the amount of bound iron
H293N
-
shows reduced enzymatic activity but no reduction in the amount of bound iron
H295N
-
shows reduced enzymatic activity but no reduction in the amount of bound iron
H101N
Methanocaldococcus jannaschii MJ0775
-
shows wild type activity
-
H200N
Methanocaldococcus jannaschii MJ0775
-
shows reduced enzymatic activity but no reduction in the amount of bound iron
-
H293N
Methanocaldococcus jannaschii MJ0775
-
shows reduced enzymatic activity but no reduction in the amount of bound iron
-
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
T85A
-
phospho-defective mutant with 67% decreased GCH-1 activity
T91A
-
phospho-defective mutant with significantly decreased GCH-1 activity
M211I
-
low activity at 0.1 mM GTP
additional information
-
wild-type and transgenic human GTPCH-overexpressing murine donor hearts are transplanted into BALB/c recipient mice via pronuclear injection of oocytes. Cardiac myocyte GTPCH overexpression inhibits cardiac graft rejection, phenotype, overview
additional information
-
S81D mutant produced significantly more NO than cells transfected with either wild type or S81A GTPCH-1
H295N
Methanocaldococcus jannaschii MJ0775
-
shows reduced enzymatic activity but no reduction in the amount of bound iron
-
additional information
-
construction of transgenic mice overexpressing the enzyme specifically in the skin together with phenylalanine hydroxylase, the clearance of phenylalanine from blood is increased in transgenic mice, measured in those with phenylketonuria, mice genotyping, overview
additional information
Q05915
construction of transgenic tomato plants expressing GCHI for engineering of the pteridine branch of folate synthesis in Lycopersicon esculentum by folate biofortification, the transgenic plants accumulate increased levels of folate after application of exogenous 4-aminobenzoate, overview
additional information
-
GTP cyclohydrolase feedback regulatory protein overexpression and knockdown in tet-GCH cells does not alter GTPCH activity or tetrahydrobiopterin levels, and GTPCH-specific knockdown in sEnd.1 endothelial cells has no effect on GTP cyclohydrolase feedback regulatory protein
additional information
-
wild-type and transgenic human GTPCH-overexpressing murine donor hearts are transplanted into BALB/c recipient mice via pronuclear injection of oocytes. Cardiac myocyte GTPCH overexpression inhibits cardiac graft rejection, phenotype, overview
additional information
Mus musculus C57BL6
-
wild-type and transgenic human GTPCH-overexpressing murine donor hearts are transplanted into BALB/c recipient mice via pronuclear injection of oocytes. Cardiac myocyte GTPCH overexpression inhibits cardiac graft rejection, phenotype, overview
-
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
reconstitution of dissociated mutant enzyme subunits to chimeric dimers from 2 monomers A and B derived from 2 different mutants, overview
-
denaturation of the purified recombinant enzyme by 4 M guanidine hydrochloride for 30 min, refolding of denatured enzyme by 100fold dilution in presence of GroE, a chaperone protein, effects of ZnSO4 and EGTA on refolding and activity
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
molecular biology
D8FT24, E4NKN2, P48596
mutations in Punch can act as genetic enhancers of Dube3a overexpression phenotypes; mutations in Punch can act as genetic enhancers of Dube3a over-expression phenotypes
medicine
-
mutations in GCH are associated with dopa-responsive dystonia and hyperphenylalaninemia
medicine
-
endothelium-specific GTPCH I overexpression retards the progression of hypertension through preservation of the structure and function of resistance mesenteric arteries, endothelium-specific GTPCH I overexpression abrogates superoxide anion production and preserves endothelial nitric oxide synthase phosphorylation, which results in preserved structural and functional integrity of resistance mesenteric arteries and lowered blood pressure in low-renin hypertension
medicine
-
the mutation in the intron 5 splicing site of the GCH1 gene, IVS5+3insT, causes Dopa-responsive dystonia (also known as Segawa syndrome or hereditary progressive dystonia with diurnal fluctuation)
biotechnology
-
creation of a phenylalanine sink by transgenic overexpression of phenylalnine hydroxylase and GTP cyclohydrolase I in the skin to reduce high phenylalanine concentrations in the blood in phenylketonuria metabolic disease
biotechnology
Q05915
construction of transgenic tomato plants expressing GCHI for engineering of the peteridine branch of folate synthesis in Lycopersicon esculentum by folate biofortification, overview
nutrition
Q05915
construction of transgenic tomato plants expressing GCHI for engineering of the peteridine branch of folate synthesis in Lycopersicon esculentum by folate biofortification, overview