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Information on EC 4.1.1.23 - orotidine-5'-phosphate decarboxylase and Organism(s) Homo sapiens and UniProt Accession P11172
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4.1.1.23 orotidine-5'-phosphate decarboxylaseIUBMB Comments
The enzyme from higher eukaryotes is identical with EC 2.4.2.10 orotate phosphoribosyltransferase .
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Word Map
- 4.1.1.23
- pyrimidine
-
phosphoribosyltransferase
- uracil
-
auxotrophic
- dihydroorotase
-
5-fluoroorotic
-
2.4.2.10
-
phosphoribosyl
- 6-azauridine
- pyrazofurin
-
transcarbamoylase
-
carbanions
- oprtase
-
aciduria
- 5-fluorouridine
- dianion
-
prototrophy
-
barbituric
-
succinate-grown
- phosphite
-
phosphodianion
-
pyre
- molecular biology
- pharmacology
- medicine
- biotechnology
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
odcase, ump synthase, orotidine 5'-monophosphate decarboxylase, orotidine-5'-phosphate decarboxylase, omp decarboxylase, orotidine-5'-monophosphate decarboxylase, ompdc, orotidine monophosphate decarboxylase, orotidylate decarboxylase, orotidine 5'-phosphate decarboxylase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Decarboxylase, orotidine 5'-phosphate
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ODCase
OMP decarboxylase
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-
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OMP-DC
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OMPDCase
OMPdecase
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Orotate decarboxylase
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-
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Orotate monophosphate decarboxylase
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-
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Orotic decarboxylase
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Orotidine 5'-monophosphate decarboxylase
Orotidine 5'-phosphate decarboxylase
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Orotidine monophosphate decarboxylase
Orotidine phosphate decarboxylase
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Orotidine-5'-monophosphate decarboxylase
Orotidylate decarboxylase
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Orotidylic acid decarboxylase
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-
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Orotidylic decarboxylase
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Orotodylate decarboxylase
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-
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UMP synthase
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Uridine 5'-monophosphate synthase
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-
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ODCase
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-
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OMPDCase
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Orotidine 5'-monophosphate decarboxylase
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Orotidine monophosphate decarboxylase
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Orotidine-5'-monophosphate decarboxylase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decarboxylation
decarboxylation
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
orotidine-5'-phosphate carboxy-lyase (UMP-forming)
The enzyme from higher eukaryotes is identical with EC 2.4.2.10 orotate phosphoribosyltransferase .
CAS REGISTRY NUMBER
COMMENTARY
9024-62-8
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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
6-cyano-UMP + H2O
beta-D-ribofuranosylbarbiturate 5'-monophosphate + CN-
-
hydrolysis
-
-
?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
-
pseudohydrolysis process
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-
?
Orotidine 5'-phosphate
UMP + CO2
UMP synthase is a bifunctional enzyme that catalyzes the penultimate and last steps in the de novo biosynthesis of UMP, the bifunctional enzyme combines the orotate phosphoribosyltransferase and the orotidine-5'-monophosphate decarboxylase activities on a single polypeptide chain
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-
?
Orotidine 5'-phosphate
UMP + CO2
the decarboxylase shows an extremely fast rate acceleration
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-
?
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
Orotidine 5'-phosphate
UMP + CO2
UMP synthase is a bifunctional enzyme that catalyzes the penultimate and last steps in the de novo biosynthesis of UMP, the bifunctional enzyme combines the orotate phosphoribosyltransferase and the orotidine-5'-monophosphate decarboxylase activities on a single polypeptide chain
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate
i.e. CMP-N3-oxide
6-amino-5-fluorouridine
-
competitive inhibition at submicromolar concentrations
6-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
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reversible inhibitor
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000295
orotidine 5'-phosphate
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orotidine-5'-phosphate decarboxylase domain of the bifunctional enzyme UMP synthase
0.0017
orotidine 5'-phosphate
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in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.028
(5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate
pH 7.5, 22°C
0.759
5-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
-
in 50 mM Tris, pH 7.5, 20 mM dithiothreitol, and 40 mM NaCl, at 55°C
4
6-amido-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
-
Ki above 4 mM, in 50 mM Tris, pH 7.5, 20 mM dithiothreitol, and 40 mM NaCl, at 55°C
2
6-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
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Ki above 2 mM, in 50 mM Tris, pH 7.5, 20 mM dithiothreitol, and 40 mM NaCl, at 55°C
0.204
6-cyanouridine
-
in 50 mM Tris, pH 7.5, 20 mM dithiothreitol, and 40 mM NaCl, at 55°C
0.000017
pyrazofurin-5'-monophosphate
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). UMPS_HUMAN
480
0
52222
Swiss-Prot
other Location (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure in complex with inhibitor (5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate. Compared to cytosin, the pyrimidine portion exhibits changes in the atomic arrangement. The oxygen atom migrates from N3 to N4 or the C5 position of the cytosine ring. These rearranged nucleotides are each bound to the enzyme in a 2?-endo,syn conformation
nine crystal structures of human OMPD in complex with substrate, product and nucleotide inhibitors are described
purified detagged recombinant enzyme, 5 mg/ml protein in 20 mM HEPES-NaOH, pH 7.4, sitting-drop setup, mixing with 0.1 M Tris-HCl, pH 8.0, and 1.8 M (NH4)2SO4 in a 1:1 ratio at 22°C, cryoprotection with 20%v/v glycerol in mother liquor, X-ray diffraction structure determination and analysis at 1.85-1.92 A resolution, molecular replacement using data from a highly twinned monoclinic crystal, pseudo-merohedrally twinned crystals, overview
hanging drop vapor diffusion method, using 100 mM Tris-HCl, pH 8.4, 2.12 M ammonium sulfate (enzyme in complex with barbiturate ribonucleoside-5'-monophosphate and 1-(5-monophosphoryl-beta-D-ribofuranos-1-yl)-5-cyanouracil) or using 100 mM Tris-HCl, pH 8.4, 1.4 M ammonium sulfate (enzyme in complex with pyrazofurin-5'-monophosphate)
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
orotidine-5'-phosphate decarboxylase activity of UMP synthase, at low protein concentrations remains constant for 40 min
55
-
1 min: 60% loss of the activity of the monomeric form, 10% loss of activity of the tetrameric form
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
conversion of the monomer to higher molecular weight forms is associated with increased stability
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15°C, storage of the high molecular weight forms in presence of 0.15 mM oxipurinol prevents the spontaneous dissociation which occures when these forms are stored in 50 mM potassium phosphate, pH 7.4
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged enzyme from Escherichia coli by nickel affinity chromatography, gel filtration, and ultrafiltration
using a Ni and a gel filtration column, the His6-tag is removed by thrombin digestion
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of His6-tagged GST-fusion enzyme, containing a tobacco etch virus protease site between His6-GST and the target protein, in Escherichia coli
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pharmacology
human UMP synthase enzyme may be a potential cancer drug target
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Brown, G.K.; Fox, R.M.; O'Sullivan, W.J.
Interconversion of different molecular weight forms of human erythrocyte orotidylate decarboxylase
J. Biol. Chem.
250
7352-7358
1975
Homo sapiens
Jones, M.E.
Orotidylate decarboxylase of yeast and man
Curr. Top. Cell. Regul.
33
331-342
1992
Saccharomyces cerevisiae, Homo sapiens, Mus musculus
Yablonski, M.J.; Pasek, D.A.; Han, B.D.; Jones, M.E.; Traut, T.W.
Intrinsic activity and stability of bifunctional human UMP synthase and its two separate catalytic domains, orotate phosphoribosyltransferase and orotidine-5'-phosphate decarboxylase
J. Biol. Chem.
271
10704-10708
1996
Homo sapiens
Wittmann, J.G.; Rudolph, M.G.
Pseudo-merohedral twinning in monoclinic crystals of human orotidine-5-monophosphate decarboxylase
Acta Crystallogr. Sect. D
63
744-749
2007
Homo sapiens (P11172), Homo sapiens
Poduch, E.; Wei, L.; Pai, E.F.; Kotra, L.P.
Structural diversity and plasticity associated with nucleotides targeting orotidine monophosphate decarboxylase
J. Med. Chem.
51
432-438
2008
Homo sapiens, Methanothermobacter thermautotrophicus (O26232), Methanothermobacter thermautotrophicus, Plasmodium falciparum (Q8IJH3), Plasmodium falciparum
Meza-Avina, M.E.; Wei, L.; Buhendwa, M.G.; Poduch, E.; Bello, A.M.; Pai, E.F.; Kotra, L.P.
Inhibition of orotidine 5-monophosphate decarboxylase and its therapeutic potential
Mini Rev. Med. Chem.
8
239-247
2008
Bacillus subtilis, Saccharomyces cerevisiae, Escherichia coli, Homo sapiens, Plasmodium falciparum, Plasmodium vivax, Methanococcus thermoautotrophicum
Kotra, L.P.; Pai, E.F.
Inhibition of orotidine-5-monophosphate decarboxylase--discoveries and lessons
Nucleic Acids Symp. Ser.
52
85-86
2008
Helicobacter pylori, Homo sapiens, Staphylococcus aureus, Plasmodium falciparum, Methanothermobacter thermautotrophicus (O26232)
Wittmann, J.G.; Heinrich, D.; Gasow, K.; Frey, A.; Diederichsen, U.; Rudolph, M.G.
Structures of the human orotidine-5-monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design
Structure
16
82-92
2008
Homo sapiens (P11172), Homo sapiens
Meza-Avina, M.E.; Wei, L.; Liu, Y.; Poduch, E.; Bello, A.M.; Mishra, R.K.; Pai, E.F.; Kotra, L.P.
Structural determinants for the inhibitory ligands of orotidine-5'-monophosphate decarboxylase
Bioorg. Med. Chem.
18
4032-4041
2010
Saccharomyces cerevisiae, Helicobacter pylori, Homo sapiens, Methanothermobacter thermautotrophicus, Staphylococcus aureus, Plasmodium falciparum
Lewis, M.; Meza-Avina, M.E.; Wei, L.; Crandall, I.E.; Bello, A.M.; Poduch, E.; Liu, Y.; Paige, C.J.; Kain, K.C.; Pai, E.F.; Kotra, L.P.
Novel interactions of fluorinated nucleotide derivatives targeting orotidine 5'-monophosphate decarboxylase
J. Med. Chem.
54
2891-2901
2011
Homo sapiens, Methanothermobacter thermautotrophicus
Huang, S.; Wong, F.M.; Gassner, G.T.; Wu, W.
Accelerated hydrolysis of alpha-halo and alpha-cyano pyridinium relative to uracil derivatives: a model for ODCase-catalyzed hydrolysis of 6-cyanoUMP
Tetrahedron Lett.
52
3960-3962
2011
Homo sapiens
Purohit, M.K.; Poduch, E.; Wei, L.W.; Crandall, I.E.; To, T.; Kain, K.C.; Pai, E.F.; Kotra, L.P.
Novel cytidine-based orotidine-5-monophosphate decarboxylase inhibitors with an unusual twist
J. Med. Chem.
55
9988-9997
2012
Homo sapiens (P11172), Plasmodium falciparum (Q8IJH3), Plasmodium falciparum
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