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Information on EC 3.5.4.29 - GTP cyclohydrolase IIa
for references in articles please use BRENDA:EC3.5.4.29
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EC Tree 3 Hydrolases
3.5 Acting on carbon-nitrogen bonds, other than peptide bonds
3.5.4 In cyclic amidines
3.5.4.29 GTP cyclohydrolase IIa
IUBMB Comments
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.
The enzyme appears in viruses and cellular organisms
Reaction Schemes
showSynonyms
gch iii, gtp cyclohydrolase iii, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
GCH III
GTP cyclohydrolase III
MJ0145
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
GTP + 3 H2O = 2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + 2 phosphate
GTP + 3 H2O = 2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + 2 phosphate
although phosphate is the product of the enzymes phosphohydrolase activity, diphosphate is a likely intermediate
GTP + 3 H2O = 2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + 2 phosphate
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-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of diphosphate bonds
-
-
-
-
hydrolysis of phosphoric acid anhydridehydrolysis of C-N bond
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
flavin biosynthesis II (archaea)
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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.
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CAS REGISTRY NUMBER
COMMENTARY
37289-19-3
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
beta,gamma-methylene-GTP + H2O
2-amino-5-formylamino-6-hydroxy-4-(5-phosphoribosylamino)-pyrimidine + methyl phosphonate
Substrates: -
Products: -
Products: -
?
dGTP + H2O
2-amino-5-formylamino-6-hydroxy-4-(deoxy-5-phosphoribosylamino)-pyrimidine + phosphate
Substrates: -
Products: -
Products: -
?
diphosphate + H2O
2 phosphate
Substrates: -
Products: -
Products: -
?
GTP + 3 H2O
2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + 2 phosphate
GTP + H2O
2-amino-5-formylamino-6-hydroxy-4-(5-phosphoribosylamino)-pyrimidine + phosphate
Substrates: -
Products: 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
Products: 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 + ?
Substrates: -
Products: -
Products: -
?
GTP + 3 H2O
2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + 2 phosphate
Substrates: -
Products: -
Products: -
?
GTP + 3 H2O
2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + 2 phosphate
Substrates: -
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
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
K+
Mg2+
Mn2+
7% of Mg2+ activation, 8% of Mg2+ diphosphate phosphohydrolase activation
Zn(OAc)2
21% of Mg2+ diphosphate phosphohydrolase activation
additional information
Mg2+
required for cyclohydrolase activity, maximal activity at 4 mM, no other metal supports full activity, maximal diphosphate phosphohydrolase activity in the presence of 5 mM MgCl2
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
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
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NH4+
activation of GTP cyclohydrolase activity, maximal activity at 50 mM
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.063
GTP
pH 8.0, 70°C, diphosphate phosphohydrolase activity
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.5
GTP
pH 8.0, 70°C, diphosphate phosphohydrolase activity
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8 - 9
GTP hydrolase and diphosphate phosphohydrolase activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
70
GTP hydrolase and diphosphate phosphohydrolase activity
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Highest Expressing Human Cell Lines
Cell Line Links Show AA Sequence and Transmembrane Helices (589 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotetramer
trimer
homotetramer
each monomer is composed of an N- and a C-terminal domain that adopt nearly superimposible structures, suggesting that the protein has arisen by gene duplication
homotetramer
-
each monomer is composed of an N- and a C-terminal domain that adopt nearly superimposible structures, suggesting that the protein has arisen by gene duplication
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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
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H136Q
approx. 7 and 15% of wild-type GTP cyclohydrolase and diphosphate phosphohydrolase activity, respectively
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, 50 mM TAPS/KOH, pH 8.0, 150 mM KCl, 9 weeks, 20% loss of activity
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
heating, streptomycin, Mono Q, Sephacryl, recombinant enzyme
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Graham, D.E.; Xu, H.; White, R.H.
A member of a new class of GTP cyclohydrolases produces formylaminopyrimidine nucleotide monophosphates
Biochemistry
41
15074-15084
2002
Methanocaldococcus jannaschii (Q57609)
brenda
Morrison, S.D.; Roberts, S.A.; Zegeer, A.M.; Montfort, W.R., Bandarian, V.
A new use for a familiar fold: the X-ray crystal structure of GTP-bound GTP cyclohydrolase III from Methanocaldococcus jannaschii reveals a two metal ion catalytic mechanism
Biochemistry
47
230-242
2007
Methanocaldococcus jannaschii (Q57609), Methanocaldococcus jannaschii, Methanocaldococcus jannaschii DSM 2661 (Q57609)
brenda
EXTERNAL LINKS (specific for EC-Number 3.5.4.29)
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