Information on EC 3.5.4.29 - GTP cyclohydrolase IIa

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The expected taxonomic range for this enzyme is: Methanocaldococcus jannaschii

EC NUMBER
COMMENTARY hide
3.5.4.29
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RECOMMENDED NAME
GeneOntology No.
GTP cyclohydrolase IIa
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
GTP + 3 H2O = 2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + 2 phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of diphosphate bonds
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hydrolysis of phosphoric acid anhydridehydrolysis of C-N bond
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
flavin biosynthesis II (archaea)
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Metabolic pathways
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Riboflavin metabolism
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flavin biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
GTP 8,9-hydrolase (phosphate-forming)
Requires Mg2+. This enzyme catalyses the hydrolysis of the imidazole ring of guanosine 5'-triphosphate, N7-methylguanosine 5'-triphosphate or inosine 5'-triphosphate. Xanthosine 5'-triphosphate and ATP are not substrates. It also catalyses the hydrolysis of diphosphate to form two equivalents of phosphate. Unlike GTP cyclohydrolase II (EC 3.5.4.25), this enzyme does not release formate, but does hydrolyse the diphosphate from GTP to phosphate.
CAS REGISTRY NUMBER
COMMENTARY hide
37289-19-3
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
beta,gamma-methylene-GTP + H2O
2-amino-5-formylamino-6-hydroxy-4-(5-phosphoribosylamino)-pyrimidine + methyl phosphonate
show the reaction diagram
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?
dGTP + H2O
2-amino-5-formylamino-6-hydroxy-4-(deoxy-5-phosphoribosylamino)-pyrimidine + phosphate
show the reaction diagram
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-
?
diphosphate + H2O
2 phosphate
show the reaction diagram
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-
?
GTP + 3 H2O
2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + 2 phosphate
show the reaction diagram
GTP + H2O
2-amino-5-formylamino-6-hydroxy-4-(5-phosphoribosylamino)-pyrimidine + phosphate
show the reaction diagram
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enzyme has diphosphate phosphohydrolase and GTP cyclohydrolase activities, no activity with 8-bromo-GTP, 8-azido-GTP, alpha,beta-methylene-GTP, ATP, GDP, GMP and XTP
?
GTP-gamma-S + H2O
2-amino-5-formylamino-6-hydroxy-4-(5-phosphoribosylamino)-pyrimidine + ?
show the reaction diagram
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
calcium is detected up to 10fold in molar excess of the protein. Treatment of the protein with Chelex (Na+ form) reduces the Ca2+ to 4fold excess but does not eliminate it
CoCl2
45% of Mg2+ diphosphate phosphohydrolase activation
Mn2+
7% of Mg2+ activation, 8% of Mg2+ diphosphate phosphohydrolase activation
Zn(OAc)2
21% of Mg2+ diphosphate phosphohydrolase activation
additional information
three metal ions are located in the active site, two of which occupy positions that are analogous to those occupied by divalent metal ions in the structures of a number of palm domain containing proteins, such as DNA polymerase I. Two conserved Asp residues that coordinate the metal ions, which are also found in palm domain containing proteins, are observed in GCH III. Site-directed variants (Asp->Asn) of these residues in GCH III are less active than wild-type. The third metal ion, most likely a potassium ion, is involved in substrate recognition through coordination of O6 of GTP. The arrangement of the metal ions in the active site suggests that GCH III utilizes two metal ion catalysis
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8-Azido-GTP
0.6 mM, 91% inhibition of GTP cyclohydrolase activity, 0.3 mM, 53% inhibition of diphosphate phosphohydrolase activity
8-bromo-GTP
0.1 mM, 50% inhibition of GTP cyclohydrolase activity, 0.1 mM, 64% inhibition of diphosphate phosphohydrolase activity
alpha,beta-methylene-GTP
0.06 mM, 80% inhibition of GTP cyclohydrolase activity, 0.6 mM, 33% inhibition of diphosphate phosphohydrolase activity
beta,gamma-methylene-GTP
0.6 mM, 34% inhibition of GTP cyclohydrolase activity
diphosphate
inhibition of diphosphate phosphohydrolase activity at high concentrations
GDP
more than 40% inhibition of GTP cyclohydrolase activity
GMP
more than 40% inhibition of GTP cyclohydrolase activity
GTP-gamma-S
0.6 mM, 80% inhibition of GTP cyclohydrolase activity
IMP
0.6 mM, 25% inhibition of GTP cyclohydrolase activity
methylene diphosphate
0.6 mM, 40% inhibition of GTP cyclohydrolase activity, 0.6 mM, 56% inhibition of diphosphate phosphohydrolase activity
NaF
0.06 mM, 55% inhibition of diphosphate phosphohydrolase activity
phosphate
0.6 mM, 25% inhibition of GTP cyclohydrolase activity
tripolyphosphate
0.6 mM, 50% inhibition of GTP cyclohydrolase activity, 0.05 mM, 52% inhibition of diphosphate phosphohydrolase activity
XTP
0.6 mM, 52% inhibition of GTP cyclohydrolase activity
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NH4+
activation of GTP cyclohydrolase activity, maximal activity at 50 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.054 - 0.063
GTP
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.35 - 0.5
GTP
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.39
recombinant enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8 - 9
GTP hydrolase and diphosphate phosphohydrolase activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
70
GTP hydrolase and diphosphate phosphohydrolase activity
PDB
SCOP
CATH
ORGANISM
UNIPROT
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30275
3 * 30275, deduced from nucleotide sequence
30359
3 * 30359, MALDI-TOF mass spectrometry
37000
3 * 37000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homotetramer
trimer
3 * 30275, deduced from nucleotide sequence; 3 * 30359, MALDI-TOF mass spectrometry; 3 * 37000, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
large square orthorhombic crystals containing the enzyme/GTP complex are obtained when both GTP and K+ is present in the crystallization drop and when Mg2+ is absent
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, 50 mM TAPS/KOH, pH 8.0, 150 mM KCl, 9 weeks, 20% loss of activity
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
heating, streptomycin, Mono Q, Sephacryl, recombinant enzyme
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
overexpressed in Escheriochia coli
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H136Q
approx. 7 and 15% of wild-type GTP cyclohydrolase and diphosphate phosphohydrolase activity, respectively
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