Information on EC 4.1.1.23 - Orotidine-5'-phosphate decarboxylase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY hide
4.1.1.23
-
RECOMMENDED NAME
GeneOntology No.
Orotidine-5'-phosphate decarboxylase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
orotidine 5'-phosphate = UMP + CO2
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
UMP biosynthesis I
-
-
UMP biosynthesis II
-
-
UMP biosynthesis III
-
-
pyrimidine metabolism
-
-
Pyrimidine metabolism
-
-
Metabolic pathways
-
-
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 hide
9024-62-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
strain NRRL2895(+)
SwissProt
Manually annotated by BRENDA team
strain NRRL2895(+)
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Methanobacterium thermoautotrophicus
-
UniProt
Manually annotated by BRENDA team
Methanobacterium thermoautotrophicus DSM 1053
-
UniProt
Manually annotated by BRENDA team
Methanococcus thermoautotrophicum
-
-
-
Manually annotated by BRENDA team
gene pyrG; gene pyrG
UniProt
Manually annotated by BRENDA team
no activity in Treponema pallidum
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
PAO1
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain 15C
-
-
Manually annotated by BRENDA team
strain BJ5464
-
-
Manually annotated by BRENDA team
; strain DG6, ATCC 49426
-
-
Manually annotated by BRENDA team
; strain DG6, ATCC 49426
-
-
Manually annotated by BRENDA team
strain ATCC 35405, single copy gene pyrF or TDE2110
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-(beta-D-erythrofuranosyl)-5-fluoroorotic acid
? + CO2
show the reaction diagram
-
truncated analog of the natural substrate orotidine 5'-monophosphate with enhanced reactivity towards decarboxylation. The vinyl carbanion-like transition state is stabilized by 3.5 kcal/mol by interactions with the 5-F substituent. Decarboxylation is activated by exogenous phosphite dianion, but the 5-F substituent results in only a 0.8 kcal stabilization of the transition state for the phosphite-activated reaction
-
-
?
1-(beta-D-erythrofuranosyl)orotic acid
?
show the reaction diagram
-
truncated substrate
-
-
?
2'-deoxyorotidine 5'-phosphate
2'-deoxyuridine 5'-phosphate + CO2
show the reaction diagram
4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
show the reaction diagram
5'-deoxy-5-fluoroorotidine
? + CO2
show the reaction diagram
-
truncated analog of the natural substrate orotidine 5'-monophosphate with enhanced reactivity towards decarboxylation. The 4'-CH3 and 4'-CH2OH groups of 5'-deoxy-5-fluoroorotidine and orotidine, respectively, result in identical destabilizations of the transition state for the unactivated decarboxylation of 2.9 kcal/mol. By contrast, the 4'-CH3 group of 5'-deoxy-5-fluoroorotidine and the 4'-CH2OH group of orotidine result in very different 4.7 and 8.3 kcal/mol destabilizations of the transition state for the phosphite-activated decarboxylation
-
-
?
5-Azaorotidine 5'-phosphate
5-Azauridine 5'-phosphate + CO2
show the reaction diagram
-
-
-
-
-
5-Fluoroorotidine 5'-phosphate
5-Fluorouridine 5'-phosphate + CO2
show the reaction diagram
6-cyano-UMP
6-hydroxyuridine 5'-phosphate + UMP
show the reaction diagram
-
-
-
-
?
6-cyano-UMP
beta-D-ribofuranosylbarbiturate 5'-monophosphate
show the reaction diagram
-
hydrolysis
-
-
?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
show the reaction diagram
orotic acid
?
show the reaction diagram
extremely poor substrate
-
?
orotidine
uridine + CO2
show the reaction diagram
-
low decarboxylation activity
-
-
?
Orotidine 5'-phosphate
?
show the reaction diagram
Orotidine 5'-phosphate
UMP + CO2
show the reaction diagram
orotidine 5'-phosphate + H+
UMP + CO2
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Orotidine 5'-phosphate
?
show the reaction diagram
Orotidine 5'-phosphate
UMP + CO2
show the reaction diagram
additional information
?
-
-
the enzyme is required for 5-fluoroorotic acid toxicity
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate
1-(5'-phospho-beta-D-ribofuranosyl)barbituric acid
1-methylorotate
-
modeling of binding and structure
1-Ribosyloxipurinol 5'-phosphate
2'-deoxy-2'-fluoro-6-iodo-beta-D-uridine 5'-O-monophosphate
2'-deoxy-2'-fluoro-6-iodo-UMP
2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-cytosine
2'-deoxyuridine 5'-phosphate
-
competitive inhibition, at higher concentrations
2- thiouridine 5'-phosphate
-
mixed inhibition
3-Xanthosine 5'-phosphate
-
-
4-(2-hydroxy-4-methoxyphenyl)-4-oxobutanoic acid
-
the inhibitor molecule occupies a part of the active site that overlaps with the phosphate-binding region in the OMP- or UMP-bound complexes. The carboxyl group of the inhibitor causes a dramatic movement of the L1 and L2 loops that play a role in the recognition of the substrate and product molecules
-
4-thiouridine 5'-phosphate
-
competitive inhibition, stronger inhibitor than UMP
5,5'-dithiobis(2-nitrobenzoate)
-
-
5,6-dihydro-6-sulfonyl-OMP
-
inhibitor with high affinity for the enzyme
5,6-dihydro-6-sulfonyl-UMP
-
inhibitor with high affinity for the enzyme
5,6-dihydroorotidine 5'-phosphate
-
-
5-(2-(N-(2-Acetamidoethyl)carbamyl)ethyl)-6-azauridine 5'phosphate
-
maximal inhibition at pH 8.3
5-(2-(N-(2-Aminoethyl)carbamyl)ethyl)-6-azauridine 5'-phosphate
-
-
5-bromo-UMP
-
-
5-Bromoorotidylate
-
-
5-Chloroorotidylate
-
-
5-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
5-cyano-UMP
5-fluoro-UMP
5-fluorouracil
-
1 mM, 14% inhibition
5-iodo-UMP
-
-
5-phosphoribofuranosylallopurinol
-
-
6-amido-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
6-amino-1-methyluracil
-
modeling of binding and structure
6-amino-5-fluorouridine
6-amino-UMP
-
competitive inhibition
6-amino-uridine 5'-monophosphate
-
-
6-aminouridine 5'-monophosphate
6-aminouridine 5'-phosphate
-
-
6-aza-UMP
6-aza-uridine 5'-monophosphate
-
-
6-Azauracil
-
competitive inhibitor
6-azauridine
6-azauridine 5'-monophosphate
6-azauridine 5'-phosphate
6-azido-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
6-azido-5-fluorouridine
6-azido-UMP
6-azido-uridine 5'-monophosphate
-
-
6-azidouridine 5'-monophosphate
6-azidouridine 5'-phosphate
-
-
6-carboxyamidouridine 5'-phosphate
-
-
6-cyano-1-methyluracil
-
modeling of binding and structure
6-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
6-cyano-UMP
-
competitive inhibition
6-cyano-uridine 5'-monophosphate
-
-
6-cyanouridine
6-cyanouridine 5'-monophosphate
6-cyanouridine 5'-phosphate
6-hydroxy UMP
-
inhibits activity with orotidine and orotidine 5'-phosphate, mutant enzyme C155S
6-hydroxy-1-methyl uracil
-
modeling of binding and structure
6-hydroxymethyl-UMP
-
-
6-hydroxyUMP
-
a transition state analogue inhibitor, binding structure in complex with the enzyme, overview
6-hydroxyuridine
6-hydroxyuridine 5'-monophosphate
-
tightly binding competitive inhibitor
6-hydroxyuridine 5'-phosphate
6-iodo-UMP
-
-
6-iodouridine
6-iodouridine 5'-monophosphate
6-methyl-uridine
-
-
6-methyl-uridine 5'-monophosphate
-
-
6-methyluridine 5'-phosphate
-
-
6-thiocarboxamidouridine
6-thiocarboxamidouridine 5'-monophosphate
6-thiocarboxamidouridine 5'-phosphate
7-Ribosyloxipurinol 5'-phosphate
-
-
8-azaxanthosine 5'-phosphate
-
-
allopurinol beta-D-riboside 5'-phosphate
-
-
allopurinol-3-riboside 5'-monophosphate
-
-
barbiturate ribonucleoside 5'-monophosphate
Barbituric acid
-
mutant enzyme C155S
barbituric acid monophosphate
-
i.e. 6-hydroxy-UMP
barbituric acid ribonucleoside 5'-monophosphate
beta-D-ribofuranosylbarbiturate 5'-monophosphate
-
potent inhibitor
clevudine
D-ribose 5-phosphate
-
-
Dimethylsulfoxide
-
20% v/v, 8% inhibition
EDTA
-
10 mM, 6% inhibition; 10 mM, at 70C, weak inhibition
gemcitabine
guanidine hydrochloride
-
2 M, denaturates
Guanidine-HCl
-
2.0 M, complete inhibition
Guanidinium chloride
-
1 M, at 70C, 81.4% inhibition
nifedipine
nimodipine
Orotidine
-
mutant enzyme C155S
oxipurinol nucleotides
-
potent, competitive, bimodal. The inhibition of the enzyme by oxipurinol nucleotides is primarily responsible for the increased urinary excretion of orotic acid and orotidine in patients treated with allopurinol
oxypurinol 5'-phosphate
-
-
phosphate
poly(ADP-D-ribose)n-1
-
-
-
potassium phosphate
-
-
pyrazofurin
pyrazofurin 5'-monophosphate
pyrazofurin-5'-monophosphate
ribose 5-phosphate
SDS
-
1%, at 70C, complete inactivation; 1%, complete inhibition
thiopurinol 5'-phosphate
-
-
Uracil
-
strong feedback inhibition
Xanthosine
xanthosine 5'-monophosphate
xanthosine 5'-phosphate
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoate)
-
0.1 mM, 2.2fold stimulation
5,5'-dithiobis(2-nitrobenzoic acid)
-
0.1 mM, at 70C, 2.2fold activation
6-Azauracil
-
1 mM, 1.2fold activation
HPO32-
-
decarboxylation of substrate analog 5'-deoxy-5-fluoroorotidine is activated. Decarboxylation of truncated substrate analog 1-(beta-D-erythrofuranosyl)-5-fluoroorotic acid is activated by exogenous phosphite dianion, but the 5-F substituent results in only a 0.8 kcal stabilization of the transition state for the phosphite-activated reaction
N-ethylmaleimide
-
10 mM, 18fold stimulation; 10 mM, at 70C, 17.8fold activation
orotidine 5'-phosphate
-
the 5'-phosphate group of the substrate activates the enzyme 240000000fold. The binding of orotidine 5'-monophosphate is accompanied by a conformational change of the enzyme from an open, inactive conformation to a closed, active conformation. As the substrate traverses the reaction coordinate to form the stabilized vinyl carbanion/carbene intermediate, interactions that destabilize the carboxylate group of the substrate and stabilize the intermediate are enforced. The activation is equivalently described by an intrinsic binding energy of 11.4 kcal/mol. The residues that directly contact the 5'-phosphate group, participate in a hydrophobic cluster near the base of the active site loop that sequesters the bound substrate from the solvent, or that form hydrogen bonding interactions across the interface between the mobile and fixed half-barrel domains of the (beta/alpha)8-barrel structure. The data support a model in which the intrinsic binding energy provided by the 5'-phosphate group is used to allow interactions both near the N-terminus of the active site loop and across the domain interface that stabilize the complexes of the enzyme in the active closed conformation with the substrate or with the substrate intermediate with the destabilized carboxylate group relative to the complex of the enzyme in the open inactive conformation with the substrate
phosphite dianion
-
activates
Uracil
-
1 mM, 1.3fold stimulation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0052 - 0.01
2'-deoxyorotidine 5'-phosphate
0.02
4-Thioorotidine 5'-phosphate
-
-
0.03
5-Azaorotidine 5'-phosphate
-
-
0.0008 - 0.41
5-Fluoroorotidine 5'-phosphate
0.0007
Orotidine
-
pH 7.2, 23C, mutant enzyme C155S
0.0016 - 0.13
orotidine 5'-monophosphate
0.0002 - 30
orotidine 5'-phosphate
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0017 - 0.16
2'-deoxyorotidine 5'-phosphate
9
4-Thioorotidine 5'-phosphate
Saccharomyces cerevisiae
-
-
5
5-Azaorotidine 5'-phosphate
Saccharomyces cerevisiae
-
-
29 - 570
5-Fluoroorotidine 5'-phosphate
22
Orotidine
Saccharomyces cerevisiae
-
pH 7.2, 23C, mutant enzyme C155S
0.042 - 21
orotidine 5'-monophosphate
0.000007 - 44
orotidine 5'-phosphate
additional information
additional information
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3 - 26
1-(beta-D-erythrofuranosyl)orotic acid
195000
160 - 12000
5-Fluoroorotidine 5'-phosphate
9073
0.00004 - 15000
orotidine 5'-phosphate
742
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.022 - 0.028
(5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate
0.00001
1-(5'-phospho-beta-D-ribofuranosyl)barbituric acid
-
below
0.26
2'-deoxyuridine 5'-phosphate
-
pH 7.4, 25C
0.043
2-thiouridine 5'-phosphate
-
pH 7, 25C
0.015
4-thiouridine 5'-phosphate
-
pH 7, 25C
0.0208
5,6-dihydro-6-sulfonyl-OMP
-
pH 7.2
0.0292
5,6-dihydro-6-sulfonyl-UMP
-
pH 7.2
0.36 - 0.759
5-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
9.1 - 550
5-cyano-UMP
0.67
5-fluoro-UMP
-
-
3.322 - 4
6-amido-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
0.00084
6-amino-UMP
-
pH 7.5, 55C
0.0021
6-amino-uridine 5'-monophosphate
-
-
0.00084
6-aminouridine 5'-monophosphate
0.0124 - 0.14
6-aza-UMP
0.0011
6-aza-uridine 5'-monophosphate
-
-
0.000012
6-azauridine 5'-monophosphate
-
-
0.000029 - 0.039
6-azauridine 5'-phosphate
0.002
6-azido-uridine 5'-monophosphate
-
-
0.00019 - 0.002
6-azidouridine 5'-monophosphate
0.00132
6-carbamoyl-UMP
-
in 50 mM Tris, pH 7.5, 20 mM dithiothreitol, and 40 mM NaCl, at 55C
0.037 - 2
6-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
0.029
6-cyano-UMP
-
pH 7.5, 55C
0.026
6-cyano-uridine 5'-monophosphate
-
-
0.0286 - 0.204
6-cyanouridine
0.011 - 0.029
6-cyanouridine 5'-phosphate
0.000000008 - 0.000094
6-hydroxyuridine 5'-phosphate
0.0341
6-methyl-uridine 5'-monophosphate
-
-
0.134
6-methyluridine 5'-phosphate
-
-
0.0000035
6-thiocarboxamidouridine 5'-phosphate
-
recombinant ODCase expressed in Escherichia coli
0.00012
8-azaxanthosine 5'-phosphate
-
-
0.004
allopurinol beta-D-riboside 5'-phosphate
-
-
0.00024
allopurinol-3-riboside 5'-monophosphate
-
-
3.5 - 4.3
AMP
0.000000009
barbiturate ribonucleoside 5'-monophosphate
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22C
1.2 - 1.4
CMP
0.081
D-ribose 5-phosphate
-
pH 7.4, 25C
7.4 - 10
dAMP
2.1 - 4.2
GMP
4 - 7.2
IMP
0.000052
oxypurinol 5'-phosphate
-
-
0.7
phosphate
0.0000036
pyrazofurin 5'-monophosphate
-
-
0.000005 - 0.0062
pyrazofurin-5'-monophosphate
37
ribose
-
pH 7.4, 25C
0.08 - 0.5
ribose 5-phosphate
0.0025
thiopurinol 5'-phosphate
-
-
3.3 - 10
TMP
0.092 - 0.5
UMP
0.0000044
xanthosine 5'-monophosphate
-
-
0.00041 - 0.73
xanthosine 5'-phosphate
0.0007 - 0.13
XMP
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1
5-bromo-UMP
Homo sapiens
-
-
0.32
5-fluoro-UMP
Homo sapiens
-
-
0.25
5-iodo-UMP
Homo sapiens
-
-
0.45
6-hydroxymethyl-UMP
Homo sapiens
-
no complete inhibition
0.0044 - 0.01
6-iodo-UMP
0.0044 - 0.0062
6-iodouridine 5'-monophosphate
0.5305
6-methyl-uridine
Plasmodium falciparum
-
-
0.4
UMP
Homo sapiens
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00018
-
below, K93A mutant
0.00047
-
below, D96A muatnt
0.00066
-
below, D91A mutant
0.0017
-
-
0.0124
-
pH 8.0, 70C
0.19
-
K59A mutant
12.4
-
pH 8.5, 70C
27.2
-
22C, native ODCase expressed in yeast
39.3
-
22-25C, pH 7.2, recombinant ODCase expressed in Escherichia coli
84
-
Q215A mutant
90
-
wild-type enzyme
additional information