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Information on EC 6.3.4.18 - 5-(carboxyamino)imidazole ribonucleotide synthase and Organism(s) Escherichia coli and UniProt Accession P09029
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6.3.4.18 5-(carboxyamino)imidazole ribonucleotide synthaseIUBMB Comments
In Escherichia coli, this enzyme, along with EC 5.4.99.18, 5-(carboxyamino)imidazole ribonucleotide mutase, is required to carry out the single reaction catalysed by EC 4.1.1.21, phosphoribosylaminoimidazole carboxylase, in vertebrates. Belongs to the ATP grasp protein superfamily . Carboxyphosphate is the putative acyl phosphate intermediate. Involved in the late stages of purine biosynthesis.
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The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
Synonyms
n5-cair synthetase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
additional information
-
PurK is a member of the ATP-grasp protein superfamily
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -
SYSTEMATIC NAME
IUBMB Comments
5-amino-1-(5-phospho-D-ribosyl)imidazole:carbon-dioxide ligase (ADP-forming)
In Escherichia coli, this enzyme, along with EC 5.4.99.18, 5-(carboxyamino)imidazole ribonucleotide mutase, is required to carry out the single reaction catalysed by EC 4.1.1.21, phosphoribosylaminoimidazole carboxylase, in vertebrates. Belongs to the ATP grasp protein superfamily [3]. Carboxyphosphate is the putative acyl phosphate intermediate. Involved in the late stages of purine biosynthesis.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 5-amino-1(5-phospho-D-ribosyl)imidazole + HCO3-
ADP + phosphate + 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole + HCO3-
ADP + 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole + phosphate
-
assay at pH 7.5, 37°C
-
-
?
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole + HCO3-
ADP + phosphate + 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole
-
-
-
-
?
ATP + 5-amino-1(5-phospho-D-ribosyl)imidazole + HCO3-
ADP + phosphate + 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole
-
-
-
-
?
ATP + 5-amino-1(5-phospho-D-ribosyl)imidazole + HCO3-
ADP + phosphate + 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole
-
catalytic steps are the formation of an acyl phosphate intermediate upon ATP cleavage, followed by the nucleophilic attack on the carboxyl carbon of the intermediates by the amino nitrogen of the mononucleotides, formation of acyl phosphate intermediates
-
-
?
additional information
?
-
-
the purEK operon is regulated by the purR gene product
-
-
?
additional information
?
-
-
comparison of active site organization and reaction mechanism to purT-encoded glycinamide ribonucleotide formyltransferase, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 5-amino-1(5-phospho-D-ribosyl)imidazole + HCO3-
ADP + phosphate + 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole
-
-
-
-
?
additional information
?
-
-
the purEK operon is regulated by the purR gene product
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-bromo-1-([3-[(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methyl]imidazolidin-1-yl]methyl)-1H-indole-2,3-dione
-
-
-
5-[(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)carbamoyl]-4-(trifluoromethyl)pyridin-2-olate
-
class I inhibitor
ethyl 4-(2-[[(4-chlorophenyl)sulfonyl]methyl]-1,3-thiazol-4-yl)-1,2-oxazole-3-carboxylate
-
-
ethyl 4-(2-[[(4-chlorophenyl)sulfonyl]methyl]-1,3-thiazol-4-yl)-5-methyl-1,2-oxazole-3-carboxylate
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-1,3-dimethyl-1H-pyrazole-5-carboxamide
-
-
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-1-methyl-1H-pyrazole-5-carboxamide
-
class I inhibitor
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-6-methoxy-4-(trifluoromethyl)pyridine-3-carboxamide
-
-
additional information
-
high-throughput screening for enzyme inhibitors, identification of inhibitor separated into three classes: class I contains compounds with an indenedione core. Class II contains an indolinedione group, and class III contains compounds that are structurally unrelated to other inhibitors in the group, overview
-
1,1'-(imidazolidine-1,3-diyldimethanediyl)bis(1H-indole-2,3-dione)
-
class II inhibitor
1-deoxy-1-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)pentitol
-
-
1-deoxy-1-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)pentitol
-
noncompetitive, class III inhibitor
2-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)-N,N-diethylacetamide
-
noncompetitive, class II inhibitor
2-hydroxy-2-[(4-methyl-1,2,5-oxadiazol-3-yl)amino]-1H-indene-1,3(2H)-dione
-
-
2-hydroxy-2-[(4-methyl-1,2,5-oxadiazol-3-yl)amino]-1H-indene-1,3(2H)-dione
-
class I inhibitor
ethyl 1-[(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methyl]piperidine-4-carboxylate
-
-
ethyl 1-[(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methyl]piperidine-4-carboxylate
-
class II inhibitor
ethyl 4-(2-[[(4-chlorophenyl)sulfonyl]methyl]-1,3-thiazol-4-yl)-5-methyl-1,2-oxazole-3-carboxylate
-
-
ethyl 4-(2-[[(4-chlorophenyl)sulfonyl]methyl]-1,3-thiazol-4-yl)-5-methyl-1,2-oxazole-3-carboxylate
-
class III inhibitor
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-2-methyl-1,3-thiazole-4-carboxamide
-
-
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-2-methyl-1,3-thiazole-4-carboxamide
-
class I inhibitor
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-4-methoxythiophene-3-carboxamide
-
-
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-4-methoxythiophene-3-carboxamide
-
class I inhibitor
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-9-oxo-9H-fluorene-4-carboxamide
-
-
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-9-oxo-9H-fluorene-4-carboxamide
-
class I inhibitor
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetics of recombinant mutant proteins, overview
-
0.0103
5-amino-1(5-phospho-D-ribosyl)imidazole
-
pH 8.0, 25°C, chimeric mutant with PurK activity
0.066
5-amino-1(5-phospho-D-ribosyl)imidazole
-
pH 8.0, 25°C, wild-type PurK
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
130
5-amino-1(5-phospho-D-ribosyl)imidazole
-
pH 8.0, 25°C, chimeric mutant with PurK activity
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
1-deoxy-1-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)pentitol
additional information
1-deoxy-1-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)pentitol
-
0.081 mM with fixed ATP and bicarbonate concentrations, 0.122 mM with fixed aminoimidazole ribonucleotide and bicarbonate concentrations
additional information
2-(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)-N,N-diethylacetamide
-
0.029 mM with fixed ATP and bicarbonate concentrations, 0.04 mM with fixed aminoimidazole ribonucleotide and bicarbonate concentrations
additional information
ethyl 4-(2-[[(4-chlorophenyl)sulfonyl]methyl]-1,3-thiazol-4-yl)-1,2-oxazole-3-carboxylate
-
0.062 mM with fixed ATP and bicarbonate concentrations, 0.043 mM with fixed aminoimidazole ribonucleotide and bicarbonate concentrations
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.069
1,1'-(imidazolidine-1,3-diyldimethanediyl)bis(1H-indole-2,3-dione)
Escherichia coli
-
-
0.02
1-deoxy-1-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)pentitol
Escherichia coli
-
-
0.0023
2-hydroxy-2-[(4-methyl-1,2,5-oxadiazol-3-yl)amino]-1H-indene-1,3(2H)-dione
Escherichia coli
-
-
0.022
ethyl 1-[(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methyl]piperidine-4-carboxylate
Escherichia coli
-
-
0.01
ethyl 4-(2-[[(4-chlorophenyl)sulfonyl]methyl]-1,3-thiazol-4-yl)-1,2-oxazole-3-carboxylate
Escherichia coli
-
-
0.0078
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-1,3-dimethyl-1H-pyrazole-5-carboxamide
Escherichia coli
-
-
0.0056
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-2-methyl-1,3-thiazole-4-carboxamide
Escherichia coli
-
-
0.017
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-4-methoxythiophene-3-carboxamide
Escherichia coli
-
-
0.017
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-6-methoxy-4-(trifluoromethyl)pyridine-3-carboxamide
Escherichia coli
-
-
0.0087
N-(2-hydroxy-1,3-dioxo-2,3-dihydro-1H-inden-2-yl)-9-oxo-9H-fluorene-4-carboxamide
Escherichia coli
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
metabolism
-
the enzyme is involved in the de novo purine biosynthetic pathway
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
comparison of tertiary structure and active site organization to purT-encoded glycinamide ribonucleotide formyltransferase, PurK shows a three domain structure
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapour diffusion of native enzyme, crystals of the native enzyme belong to space group C222(1) with unit cell dimensions of a = 93.4 A, b = 95.2 A and c = 120.6 A. Crystals of the enzyme/MgADP complex are grown by batch methods at room temperature with poly(ethylene glycol)8000 as precipitant. The crystals belong to the space group P1 with unit cell dimensions of a = 60.6 A, b = 92.1 A, c = 102.6 A, alpha = 66.1°, beta = 82.7° and gamma = 81.8°
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
generation of six recombinant hybrid proteins combining functional domains of PurK and PurT, glycinamide ribonucleotide formyltransferase, on the basis of structural and sequence alignments, overview. The mutant chimeras are functional and show activity with different substrates, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Meyer, E.; Leonard, N.J.; Bhat, B.; Stubbe, J.; Smith, J.M.
Purification and characterization of the purE, purK, and purC gene products: identification of a previously unrecognized energy requirement in the purine biosynthetic pathway
Biochemistry
31
5022-5032
1992
Escherichia coli
Mueller, E.J.; Meyer, E.; Rudolph, J.; Davisson, V.J.; Stubbe, J.
N5-carboxyaminoimidazole ribonucleotide: evidence for a new intermediate and two new enzymatic activities in the de novo purine biosynthetic pathway of Escherichia coli
Biochemistry
33
2269-2278
1994
Escherichia coli
Thoden, J.B.; Kappock, T.J.; Stubbe, J.; Holden, H.M.
Three-dimensional structure of N5-carboxyaminoimidazole ribonucleotide synthetase: a member of the ATP grasp protein superfamily
Biochemistry
38
15480-15492
1999
Escherichia coli (P09029)
Watanabe, W.; Sampei, G.; Aiba, A.; Mizobuchi, K.
Identification and sequence analysis of Escherichia coli purE and purK genes encoding 5'-phosphoribosyl-5-amino-4-imidazole carboxylase for de novo purine biosynthesis
J. Bacteriol.
171
198-204
1989
Escherichia coli, Escherichia coli NK6051
Tiedeman, A.A.; Keyhani, J.; Kamholz, J.; Daum, H.A., 3rd; Gots, J.S.; Smith, J.M.
Nucleotide sequence analysis of the purEK operon encoding 5'-phosphoribosyl-5-aminoimidazole carboxylase of Escherichia coli K-12
J. Bacteriol.
171
205-212
1989
Escherichia coli
Firestine, S.M.; Paritala, H.; McDonnell, J.E.; Thoden, J.B.; Holden, H.M.
Identification of inhibitors of N5-carboxyaminoimidazole ribonucleotide synthetase by high-throughput screening
Bioorg. Med. Chem.
17
3317-3323
2009
Escherichia coli
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