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Information on EC 3.5.4.16 - GTP cyclohydrolase I and Organism(s) Escherichia coli and UniProt Accession P0A6T5

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IUBMB 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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Escherichia coli
UNIPROT: P0A6T5
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The taxonomic range for the selected organisms is: Escherichia coli
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
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dihydroneopterin triphosphate synthase
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-
-
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GCYH-IA
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GTP 8-formylhydrolase
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GTP CHase I
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GTP cyclohydrolase
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GTP cyclohydrolase I
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GTP-CH-I
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GTPCH I
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guanosine triphosphate 8-deformylase
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guanosine triphosphate cyclohydrolase
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guanosine triphosphate cyclohydrolase I
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hydrolase, guanosine triphosphate cyclo-
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Punch protein
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
reaction mechanism, active site structure, GTP binding strcuture
GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
amidine hydrolysis
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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 hide
37289-19-3
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
substrate is the reaction intermediate of the overall reaction
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
beta-gamma-methyleneguanosine 5'-triphosphate + H2O
beta-gamma-methylene-7,8-dihydroneopterin 3'-triphosphate + formate
show the reaction diagram
-
-
-
?
GTP + H2O
2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone triphosphate + ?
show the reaction diagram
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mutant H179N is not able to perform the whole reaction step
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-
r
GTP + H2O
dihydroneopterin triphosphate + formate
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 + D-erythro-dihydroneopterin triphosphate
show the reaction diagram
additional information
?
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GCYH-I is not only the first enzyme of the tetrahydrofolate and tetrahydropterin pathways, but also the first enzyme of queuosine and archaeosine biosynthesis
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
-
-
-
?
GTP + H2O
dihydroneopterin triphosphate + formate
show the reaction diagram
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first step in the biosynthesis of pteridine coenzymes, such as folic acid and tetrahydrobiopterin
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-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
show the reaction diagram
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first step in the biosynthesis pathway leading to dihydrofolate and tetrahydrobiopterin
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-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
show the reaction diagram
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
show the reaction diagram
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first commited step in the biosynthesis of tetrahydrofolate and tetrahydrobiopterin
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-
?
additional information
?
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GCYH-I is not only the first enzyme of the tetrahydrofolate and tetrahydropterin pathways, but also the first enzyme of queuosine and archaeosine biosynthesis
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-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
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
Mg2+
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activates
additional information
-
no metals required
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8-Azaguanine
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43% inhibition at 2.9 mM
8-ethoxycarbonyl-7-deazaguanine
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78% inhibition at 2.9 mM
8-methyl-7-deazaguanine
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94% inhibition at 2.9 mM
8-trifluoromethyl-7-deazaguanine
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17% inhibition at 2.9 mM
ADP
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competitive inhibitor
ascorbate
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guanosine 5'-tetraphosphate
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L-erythro-5,6,7,8-tetrahydrobiopterin
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UTP reduces inhibition
PO43-
tetrahydrobiopterin
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feedback inhibition
TTP
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competitive inhibitor
additional information
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synthesis and inhibitory potential of 7-deazaguanine derivatives on GTPCH I, inhibitory mechanism, overview
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0001
0.088
wild-type enzyme, substrate 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone triphosphate
0.091
wild-type enzyme, substrate GTP
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
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mutant S135C
7 - 8.5
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mutant V150E
7.5
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mutant H112D
9
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mutant E152K
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
26
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assay at
45
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mutant E152K
55
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mutants S135C and R185G
60
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wild-type enzyme and mutant R139C
65
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mutants H112D, K136E, and H179Q
70
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mutant H113 N
72
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mutant R56L
75
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mutants C110G and L134Q
85
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mutants E111K and V150E
90
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mutant C181S
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
Uniprot
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
120000
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wild-type enzyme in presence of 0.3 M KCl, mutants C110G, E111K, H112D, and C181S, gel filtration
210000
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gel filtration
25000
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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
250000
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decameric wild-type enzyme, gel filtration
300000
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larger than 300000, gel filtration
50000
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dimeric mutants K136E and R139C, gel filtration
51000
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4 * 51000, SDS-PAGE
additional information
-
MW of mutant E152K is very high in gel filtration approximately corresponding to a didecameric form
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decamer
tetramer
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4 * 51000, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C110S
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
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
H112S
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
H113S
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
C110G
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site-directed mutagenesis, 0.22% activity compared to the wild-type enzyme, increased temperature optimum
C181S
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site-directed mutagenesis, 0.29% activity compared to the wild-type enzyme, highly increased temperature optimum
E111K
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site-directed mutagenesis, 3.1% activity compared to the wild-type enzyme, increased temperature optimum
E152K
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site-directed mutagenesis, 0.06% activity compared to the wild-type enzyme, increased pH optimum, decreased temperature optimum
H112D
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site-directed mutagenesis, 0.23% activity compared to the wild-type enzyme, decreased pH optimum, increased temperature optimum
H113N
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site-directed mutagenesis, 67% activity compared to the wild-type enzyme, decreased pH optimum, increased temperature optimum
H179N
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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
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site-directed mutagenesis, 0.8% activity compared to the wild-type enzyme, increased temperature optimum
K136E
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site-directed mutagenesis, 0.25% activity compared to the wild-type enzyme, increased temperature optimum
L134Q
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site-directed mutagenesis, 1.85% activity compared to the wild-type enzyme, increased temperature optimum
R139C
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site-directed mutagenesis, 29.3% activity compared to the wild-type enzyme, decreased pH optimum
R185G
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site-directed mutagenesis, 2.9% activity compared to the wild-type enzyme, decreased temperature optimum
R56L
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site-directed mutagenesis, 14% activity compared to the wild-type enzyme, increased temperature optimum
S135C
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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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
82
-
half-life: 7 min
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant wild-type and mutant enzymes
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of wild-type and mutant enzymes from plasmids in strain DH5alpha
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
reconstitution of dissociated mutant enzyme subunits to chimeric dimers from 2 monomers A and B derived from 2 different mutants, overview
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ferre, J.; Yim, J.J.; Jacobson, K.B.
Purification of guanosine triphosphate cyclohydrolase I from Escherichia coli. The use of competitive inhibitors versus substrate as ligands in affinity chromatography
J. Chromatogr.
357
283-292
1986
Escherichia coli
Manually annotated by BRENDA team
Blau, N.; Niederwieser, A.
GTP-cyclohydrolases: a review
J. Clin. Chem. Clin. Biochem.
23
169-176
1985
Geobacillus stearothermophilus, Comamonas sp., Escherichia coli, Lactiplantibacillus plantarum, Mammalia, Rattus norvegicus, Serratia indica
Manually annotated by BRENDA team
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
-
Manually annotated by BRENDA team
Ferre, J.; Jacobson, K.B.
Formation of beta,gamma-methylene-7,8-dihydroneopterin 3-triphosphate from beta,gamma-methyleneguanosine 5-triphosphate by GTP cyclohydrolase I of Escherichia coli
Arch. Biochem. Biophys.
233
475-480
1984
Escherichia coli
Manually annotated by BRENDA team
Yim, J.J.; Brown, G.M.
Characteristics of guanosine triphosphate cyclohydrolase I purified from Escherichia coli
J. Biol. Chem.
251
5087-5094
1976
Escherichia coli
Manually annotated by BRENDA team
Burg, A.W.; Brown, G.M.
The biosynthesis of folic acid. 8. Purification and properties of the enzyme that catalyzes the production of formate from carbon atom 8 of guanosine triphosphate
J. Biol. Chem.
243
2349-2358
1968
Escherichia coli
Manually annotated by BRENDA team
Schmid, C.; Ladenstein, R.; Luecke, H.; Huber, R.; Bacher, A.
Crystallization and preliminary crystallographic characterization of GTP cyclohydrolase I from Escherichia coli
J. Mol. Biol.
226
1279-1281
1992
Escherichia coli
Manually annotated by BRENDA team
Schoedon, G.; Redweik, U.; Frank, G.; Cotton, R.G.H.; Blau, N.
Allosteric characteristics of GTP cyclohydrolase I from Escherichia coli
Eur. J. Biochem.
210
561-568
1992
Escherichia coli
Manually annotated by BRENDA team
Bracher, A.; Schramek, N.; Bacher, A.
Biosynthesis of pteridines. Stopped-flow kinetic analysis of GTP cyclohydrolase I
Biochemistry
40
7896-7902
2001
Escherichia coli
Manually annotated by BRENDA team
Lee, S.; Ahn, C.; Park, E.; Hwang, D.S.; Yim, J.
Biochemical characterization of oligomerization of Escherichia coli GTP cyclohydrolase I
J. Biochem. Mol. Biol.
35
255-261
2002
Escherichia coli
Manually annotated by BRENDA team
Schramek, N.; Bracher, A.; Fischer, M.; Auerbach, G.; Nar, H.; Huber, R.; Bacher, A.
Reaction mechanism of GTP cyclohydrolase I: single turnover experiments using a kinetically competent reaction intermediate
J. Mol. Biol.
316
829-837
2002
Escherichia coli
Manually annotated by BRENDA team
Rebelo, J.; Auerbach, G.; Bader, G.; Bracher, A.; Nar, H.; Hosl, C.; Schramek, N.; Kaiser, J.; Bacher, A.; Huber, R.; Fischer, M.
Biosynthesis of pteridines. Reaction mechanism of GTP cyclohydrolase I
J. Mol. Biol.
326
503-516
2003
Escherichia coli (P0A6T5), Escherichia coli
Manually annotated by BRENDA team
Auerbach, G.; Herrmann, A.; Bracher, A.; Bader, G.; Gutlich, M.; Fischer, M.; Neukamm, M.; Garrido-Franco, M.; Richardson, J.; Nar, H.; Huber, R.; Bacher, A.
Zinc plays a key role in human and bacterial GTP cyclohydrolase I
Proc. Natl. Acad. Sci. USA
97
13567-13572
2000
Escherichia coli, Homo sapiens (P30793), Homo sapiens
Manually annotated by BRENDA team
Gibson, C.L.; La Rosa, S.; Ohta, K.; Boyle, P.H.; Leurquin, F.; Lemacon, A.; Suckling, C.J.
The synthesis of 7-deazaguanines as potential inhibitors of guanosine triphosphate cyclohydrolase I
Tetrahedron
60
943-959
2004
Escherichia coli
-
Manually annotated by BRENDA team
Phillips, G.; El Yacoubi, B.; Lyons, B.; Alvarez, S.; Iwata-Reuyl, D.; de Crecy-Lagard, V.
Biosynthesis of 7-deazaguanosine-modified tRNA nucleosides: a new role for GTP cyclohydrolase I
J. Bacteriol.
190
7876-7884
2008
Escherichia coli, Haloferax volcanii
Manually annotated by BRENDA team