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Enzyme Nomenclature
Information on EC 4.1.1.23 - orotidine-5'-phosphate decarboxylase
for references in articles please use BRENDA:EC4.1.1.23
Word Map on EC 4.1.1.23
- 4.1.1.23
- pyrimidine
-
phosphoribosyltransferase
-
decarboxylation
- uracil
-
auxotrophic
-
5-fluoroorotic
- dihydroorotase
-
2.4.2.10
-
phosphoribosyl
- 6-azauridine
- pyrazofurin
-
carbanions
-
aciduria
-
transcarbamoylase
- oprtase
-
decarboxylases
- dianion
- phosphite
-
barbituric
-
prototrophy
-
pyre
-
phosphodianion
- pharmacology
- molecular biology
- medicine
- biotechnology
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
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EC NUMBER 
COMMENTARY 
4.1.1.23
-
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RECOMMENDED NAME
GeneOntology No.
orotidine-5'-phosphate decarboxylase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
orotidine 5'-phosphate = UMP + CO2
-
-
-
-
orotidine 5'-phosphate = UMP + CO2
catalytic mechanism with freely reversible binding, a very limited contribution to the overall rate is made by chemical steps preceding decarboxylation
-
orotidine 5'-phosphate = UMP + CO2
mechanism, thermodynamic data
-
orotidine 5'-phosphate = UMP + CO2
mechanism
-
orotidine 5'-phosphate = UMP + CO2
catalytic mechanism
-
orotidine 5'-phosphate = UMP + CO2
reaction mechanism involving the active site aspartate residue Asp91, electrostatic stress furnishes the majority of the catalytic driving force for OMP decarboxylation, ylide generation is not the rate-limiting step in the ODCase reaction
-
orotidine 5'-phosphate = UMP + CO2
decarboxylation mechanism, substrate recognition mechanism with dynamic structural changes, as well as the rearrangement of the hydrogen bond array at the active site
-
orotidine 5'-phosphate = UMP + CO2
direct decarboxylation mechanism, modeling with 6-carbanion derivatives of uracil analogues, overview
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decarboxylation
decarboxylation
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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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 .
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CAS REGISTRY NUMBER
COMMENTARY
9024-62-8
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
theoretical study based on the structure of Bacillus subtilis enzyme
Uniprot
bifunctional UMP synthase contains activities of EC 2.4.2.10 and EC 4.1.1.23
-
-
-
-
-
bifunctional UMP synthase contains activities of EC 2.4.2.10 and EC 4.1.1.23
-
-
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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
1-(beta-D-erythrofuranosyl)-5-fluoroorotic acid
? + CO2
-
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
?
-
truncated substrate
-
-
?
5'-deoxy-5-fluoroorotidine
? + CO2
-
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
-
-
?
6-cyano-UMP
6-hydroxyuridine 5'-phosphate + UMP
-
-
-
-
?
2'-deoxyorotidine 5'-phosphate
2'-deoxyuridine 5'-phosphate + CO2
-
decreased catalytic rate compared with orotidine 5'-phosphate as substrate
-
?
2'-deoxyorotidine 5'-phosphate
2'-deoxyuridine 5'-phosphate + CO2
-
-
-
?
2'-deoxyorotidine 5'-phosphate
2'-deoxyuridine 5'-phosphate + CO2
-
-
-
-
?
2'-deoxyorotidine 5'-phosphate
2'-deoxyuridine 5'-phosphate + CO2
less effective than orotidine 5’-phosphate
-
?
4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
-
partially active substrate
-
?
4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
-
50% reduced kcat-value compared with orotidine 5'-phosphate as substrate
-
?
4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
-
-
-
-
-
4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
-
nearly equally effective as orotidine 5'-phosphate
-
?
4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
-
nearly equally effective as orotidine 5'-phosphate
-
?
5-Fluoroorotidine 5'-phosphate
5-Fluorouridine 5'-phosphate + CO2
-
-
-
-
-
5-Fluoroorotidine 5'-phosphate
5-Fluorouridine 5'-phosphate + CO2
-
-
-
?
5-Fluoroorotidine 5'-phosphate
5-Fluorouridine 5'-phosphate + CO2
-
-
-
-
?
5-Fluoroorotidine 5'-phosphate
5-Fluorouridine 5'-phosphate + CO2
-
the 5-fluoro substituent results in a 3400fold increase in the first-order rate constant for deuterium exchange
-
-
?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
-
pseudohydrolysis process
-
-
?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
-
-
-
-
?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
-
pseudohydrolysis process
-
-
?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
-
pseudohydrolysis process
-
-
?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
-
pseudohydrolysis process
-
-
?
Orotidine 5'-phosphate
?
-
final step in pyrimidine biosynthesis
-
-
-
Orotidine 5'-phosphate
UMP + CO2
catalytic mechanism, bimolecular electrophilic substitution mechanism in which decarboxylation and carbon-carbon bond protonation by Lys-62 occur in a concerted action, enzyme/active site structure, one active site per monomer, located near the dimer interface
-
?
Orotidine 5'-phosphate
UMP + CO2
-
mechansim, no formation of a vinyl anion intermediate, enzyme structure, the active sites are located at the dimer interface
-
?
Orotidine 5'-phosphate
UMP + CO2
catalyzes the final step in the de novo biosynthesis of uridine monophosphate
-
?
Orotidine 5'-phosphate
UMP + CO2
last common step in pyrimidine biosynthesis, constitutive expression
-
?
Orotidine 5'-phosphate
UMP + CO2
last common step in pyrimidine biosynthesis, constitutive expression
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalytic mechanism, role of Lys-93 in catalysis, enzyme structure
-
?
Orotidine 5'-phosphate
UMP + CO2
-
enzyme/active site structure, contains two independently functioning active sites, binding of the phosphoryl group of the substrate is essential for the catalytic function, induced fit mechanism
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the last step in the de novo synthesis of UMP
-
?
Orotidine 5'-phosphate
UMP + CO2
-
last step in the de novo synthesis of pyrimidine nucleotides
-
?
Orotidine 5'-phosphate
UMP + CO2
-
-
-
-
?
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
-
-
?
Orotidine 5'-phosphate
UMP + CO2
the decarboxylase shows an extremely fast rate acceleration
-
-
?
Orotidine 5'-phosphate
UMP + CO2
Methanobacterium thermoautotrophicus DSM 1053
-
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
-
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalytic mechanism, the remarkable catalytic power is almost exclusively achieved via ground state destabilization of the reactive part of substrate, which is compensated for by strong binding of the phosphate and ribose groups, and to a lesser extend via transition state stabilization, enzyme/active site structure, mode of substrate binding
-
?
Orotidine 5'-phosphate
UMP + CO2
-
mechanism involving an equilibrium pre-protonation of orotidine 5'-phosphate C5 by the catalytic Lys-72 residue that greatly reduces the barrier to subsequent decarboxylation, Lys-72 is not critical for substrate binding
-
?
Orotidine 5'-phosphate
UMP + CO2
-
mechanism, enzyme conformation is more distorted in the reactant state than in the transition state, the energy released from conformation relaxation provides the predominant contribution to the rate enhancement, the active site consists of a network of charged residues Lys-42, Asp-70, Lys-72, Asp-75b
-
?
Orotidine 5'-phosphate
UMP + CO2
-
mechanism, Lys-42, Asp-70, Lys-72 and Asp-75b form an alternate charged network around the reactive part of substrate, Lys-72 protonates the intermediate C6 carbanion
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the final step in the de novo biosynthesis of UMP
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the last step of de novo pyrimidine synthesis
-
?
Orotidine 5'-phosphate
UMP + CO2
-
last step in the biosynthesis of pyrimidine nucleotides
-
?
Orotidine 5'-phosphate
UMP + CO2
-
the enzyme catalyzes the decarboxylation of orotidine 5'-monophosphate without any covalent intermediates, active site residues in ODCase are involved in an extensive hydrogen-bonding network, active site Lys42
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
the remote 5'-phosphate group of the substrate activates the enzyme 240 millionfold, the activation corresponds to an intrinsic binding energy of 11.4 kcal/mol. This intrinsic binding energy is used to allow interactions both near the N-terminus of the active site loop and across the domain interface that stabilize both the Ec-S and Ec-S* complexes relative to the Eo-S complex
-
-
?
Orotidine 5'-phosphate
UMP + CO2
the remote 5'-phosphate group of the substrate activates the enzyme 240 millionfold, the activation corresponds to an intrinsic binding energy of 11.4 kcal/mol. This intrinsic binding energy is used to allow interactions both near the N-terminus of the active site loop and across the domain interface that stabilize both the Ec-S and Ec-S* complexes relative to the Eo-S complex
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
-
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
the sixth enzyme in the pathway catalyzing formation of uridine 5'-monophosphate
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
final step in the de novo synthesis of uridine 5'-monophosphate, UMP, defects in the enzyme are lethal in the malaria parasite
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
change in active-site structure upon binding of orotidine 5'-phosphate/UMP, the backbone amide of Arg294 interacts directly with the phosphate group of the ligands, rearrangement of hydrogen-bond network around Lys102, overview
-
-
?
Orotidine 5'-phosphate
UMP + CO2
the enzyme catalyzes the decarboxylation of orotidine 5'-monophosphate without any covalent intermediates, active site residues in ODCase are involved in an extensive hydrogen-bonding network, active site Lys42
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
-
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalytic mechanism involving protonation at O2 and a proposed Zn2+ interaction at O4, role of Lys-93 in catalysis
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalytic proficiency, activity does not depend on the formation of a covalent bond to the substrate, catalyzes the reaction through noncovalent binding interactions that involve only the functional groups of its constituent amino acids, catalytic mechanism, mechanism of transition state stabilization, active site structure, role of Lys-93
-
ir
Orotidine 5'-phosphate
UMP + CO2
-
enzyme has two functionally independent substrate binding sites
-
?
Orotidine 5'-phosphate
UMP + CO2
enzyme/active site structure, mode of substrate binding
-
?
Orotidine 5'-phosphate
UMP + CO2
-
mechanism, carbanion intermediate is stabilized by simple electrostatic interaction with Lys-93, the driving force of reaction is ground state destabilization resulting from charge repulsion between the carboxyl of the substrate and Asp-91
-
?
Orotidine 5'-phosphate
UMP + CO2
-
the integrity of the network of the charged residues within the active site, Lys-59, Asp-91, Lys-93 and Asp-96, is essential for transition state stabilization, altered substrate is very tightly bound in the transition state, mechanism
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the critical final step in the pyrimidine biosynthetic pathway
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the final step of de novo pyrimidine nucleotide biosynthesis
-
?
Orotidine 5'-phosphate
UMP + CO2
catalyzes the final step of pyrimidine biosynthesis
-
?
Orotidine 5'-phosphate
UMP + CO2
-
production of UMP, the biosynthetic precursor of pyrimidine nucleotides
-
?
Orotidine 5'-phosphate
UMP + CO2
-
the enzyme is the most effective pure protein catalyst known in nature
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
act upon its substrate without the intervention of metals or other cofactors and without the formation of covalent bonds between the enzyme and the substrate, substrate binding forces the substrate’s scissile carboxylate group into the neighborhood of several charged groups at the active site, reaction mechanism, overview
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
the decarboxylase shows an extremely fast rate acceleration, 1017-fold rate enhancement, ODCase associates weakly with the substrate in the ground state, but then tightens its grip as the altered substrate approaches the chemical transition state, yielding a complex with an estimated dissociation constant Ktx of over 10-24 M
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalytic mechanism involving protonation at O2 and a proposed Zn2+ interaction at O4, role of Lys-93 in catalysis
-
?
Orotidine 5'-phosphate
UMP + CO2
-
production of UMP, the biosynthetic precursor of pyrimidine nucleotides
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the final step of de novo pyrimidine nucleotide biosynthesis
-
?
Orotidine 5'-phosphate
UMP + CO2
-
the enzyme is required for de novo pyrimidine synthesis catalyzing the key final step in de novo synthesis of UMP
-
-
?
additional information
?
-
theoretical studies of the effect of thio substitution on orotidine monophosphate decarboxylase substrates
-
-
-
additional information
?
-
Methanobacterium thermoautotrophicus
-
computed kinetic isotope effects support a direct decarboxylation mechanism. Data suggest a role for Lys72 in stabilizing the transition state in the catalysis of orotidine 5'-phosphate and, to a somewhat lesser extent, in 5-fluoro-orotidine 5'-phosphate
-
-
-
additional information
?
-
Methanobacterium thermoautotrophicus DSM 1053
-
computed kinetic isotope effects support a direct decarboxylation mechanism. Data suggest a role for Lys72 in stabilizing the transition state in the catalysis of orotidine 5'-phosphate and, to a somewhat lesser extent, in 5-fluoro-orotidine 5'-phosphate
-
-
-
additional information
?
-
-
not: 2-thioorotidine 5'-phosphate
-
?
additional information
?
-
-
the enzyme also converts 6-cyano-UMP to barbituric acid monophosphate with low activity
-
-
-
additional information
?
-
-
the enzyme is required for 5-fluoroorotic acid toxicity
-
-
-
additional information
?
-
the enzyme is required for 5-fluoroorotic acid toxicity
-
-
-
additional information
?
-
-
2-thioorotidine 5'-phosphate is 10000000fold less reactive than orotidine 5'-phosphate as substrate, not: 2-thiouridine 5'-phosphate
-
?
additional information
?
-
-
not: 2-thioorotidine 5’-phosphate, undetectable activity with CMP-6-carboxylate and weak binding to ODCase
-
?
additional information
?
-
-
the yeast enzyme does not exhibit a measurable affinity for a substrate analogue in which the labile carboxylate group is replaced by a cationic substituent, the apo and ligand-bound forms of the enzyme show distinct open and closed forms, the closed form is catalytically competent
-
-
-
additional information
?
-
-
in reaction model phosphodianion binding interactions are utilized to stabilize a rare closed enzyme form that exhibits a high catalytic activity for decarboxylation. The thermodynamic barrier to formation of the productive catalytic complex from the inactive enzyme arises largely from the desolvation of the active site accompanying the conformational change and sequestration of the substrate from bulk solvent. The energetically unfavorable conformational change and desolvation of the active site are paid for by the binding energy available from the formation of strong phosphodianion-protein interactions in the desolvated environment present at the EC·S complex. The phosphodianion binding energy is recovered as transition state stabilization via the enhanced electrostatic and hydrogen bonding interactions at the transition state in the desolvated active site
-
-
-
additional information
?
-
-
the total transition-state stabilization for decarboxylation of orotidine 5'-phosphate via the UMP vinyl carbanion intermediate exceeds that for the formation of this carbanion by proton transfer from C-6 of UMP to the enzyme by ca.17 kcal/mol. A large portion of the total transition-state stabilization for the decarboxylation of orotidine 5'-monophosphate can be accounted for by stabilization of the enzyme-bound vinyl carbanion intermediate of the stepwise reaction
-
-
-
additional information
?
-
-
not: 2-thioorotidine 5’-phosphate, undetectable activity with CMP-6-carboxylate and weak binding to ODCase
-
?
additional information
?
-
-
the enzyme is required for 5-fluoroorotic acid toxicity
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
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
additional information
?
-
-
the enzyme is required for 5-fluoroorotic acid toxicity
-
-
-
Orotidine 5'-phosphate
?
-
final step in pyrimidine biosynthesis
-
-
-
Orotidine 5'-phosphate
UMP + CO2
P25971
catalyzes the final step in the de novo biosynthesis of uridine monophosphate
-
?
Orotidine 5'-phosphate
UMP + CO2
Q870M2
last common step in pyrimidine biosynthesis, constitutive expression
-
?
Orotidine 5'-phosphate
UMP + CO2
Q870M2
last common step in pyrimidine biosynthesis, constitutive expression
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the last step in the de novo synthesis of UMP
-
?
Orotidine 5'-phosphate
UMP + CO2
-
last step in the de novo synthesis of pyrimidine nucleotides
-
?
Orotidine 5'-phosphate
UMP + CO2
P11172
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
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
-
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the final step in the de novo biosynthesis of UMP
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the last step of de novo pyrimidine synthesis
-
?
Orotidine 5'-phosphate
UMP + CO2
-
last step in the biosynthesis of pyrimidine nucleotides
-
?
Orotidine 5'-phosphate
UMP + CO2
-
-
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
the sixth enzyme in the pathway catalyzing formation of uridine 5'-monophosphate
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
final step in the de novo synthesis of uridine 5'-monophosphate, UMP, defects in the enzyme are lethal in the malaria parasite
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
-
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the critical final step in the pyrimidine biosynthetic pathway
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the final step of de novo pyrimidine nucleotide biosynthesis
-
?
Orotidine 5'-phosphate
UMP + CO2
P03962
catalyzes the final step of pyrimidine biosynthesis
-
?
Orotidine 5'-phosphate
UMP + CO2
-
production of UMP, the biosynthetic precursor of pyrimidine nucleotides
-
?
Orotidine 5'-phosphate
UMP + CO2
-
the enzyme is the most effective pure protein catalyst known in nature
-
-
?
Orotidine 5'-phosphate
UMP + CO2
-
production of UMP, the biosynthetic precursor of pyrimidine nucleotides
-
?
Orotidine 5'-phosphate
UMP + CO2
-
catalyzes the final step of de novo pyrimidine nucleotide biosynthesis
-
?
Orotidine 5'-phosphate
UMP + CO2
-
the enzyme is required for de novo pyrimidine synthesis catalyzing the key final step in de novo synthesis of UMP
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no cofactors are involved in catalysis
-
additional information
-
ODCase contains no small molecule cofactors
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zinc
Zn2+
additional information
Zinc
-
zinc, rather than a proton may be largely responsible for neutralizing charge development in the transition state for OMP decarboxylation
Zn2+
-
mechanism may include participation of Zn2+, which interacts at O4 with the substrate
Zn2+
-
native ODCase expressed in yeast contains zinc, but not recombinant ODCase expressed in Escherichia coli, zinc is not involved in substrate decarboxylation
additional information
-
no metals are involved in catalysis
additional information
-
ODCase contains no metal ions
additional information
-
no metal cofactor, e.g. Zn2+ or other transition metal ions
additional information
-
zinc-free fully active recombinant ODCase expressed in Escherichia coli, metals do not directly participate in the decarboxylation mechanism
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate
2'-deoxyuridine 5'-phosphate
-
competitive inhibition, at higher concentrations
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
5,6-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-(2-(N-(2-Acetamidoethyl)carbamyl)ethyl)-6-azauridine 5'phosphate
-
maximal inhibition at pH 8.3
6-amino-1-methyluracil
-
modeling of binding and structure
6-cyano-1-methyluracil
-
modeling of binding and structure
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-hydroxyUMP
-
a transition state analogue inhibitor, binding structure in complex with the enzyme, overview
6-hydroxyuridine 5'-monophosphate
-
tightly binding competitive inhibitor
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
(5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate
-
i.e. CMP-N3-oxide
(5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate
i.e. CMP-N3-oxide
1-(5'-phospho-beta-D-ribofuranosyl)barbituric acid
-
high affinity inhibitor
1-Ribosyloxipurinol 5'-phosphate
-
most effective oxipurinol nucleotide inhibitor
2'-deoxy-2'-fluoro-6-iodo-beta-D-uridine 5'-O-monophosphate
-
-
2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-cytosine
-
-
5-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
-
-
6-amido-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
-
poor inhibitor
6-amino-5-fluorouridine
-
competitive inhibition at submicromolar concentrations
6-amino-5-fluorouridine
-
competitive inhibition at submicromolar concentrations
6-azido-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
-
-
6-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
-
reversible inhibitor
6-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
-
reversible inhibitor
6-iodouridine 5'-monophosphate
-
i.e. 6-iodo-UMP, irreversible inhibition, mass spectral analysis of the enzyme-inhibitor complex, binding to the enzyme is accompanied by loss of two protons and the iodo moiety, covalent bond formation
6-iodouridine 5'-monophosphate
-
irreversible inhibitor
6-iodouridine 5'-monophosphate
-
i.e. 6-iodo-UMP, irreversible inhibition, mass spectral analysis of the enzyme-inhibitor complex, binding to the enzyme is accompanied by loss of two protons and the iodo moiety, covalent bond formation, the inhibitor exhibits potent antiplasmodial activity
6-thiocarboxamidouridine 5'-phosphate
-
competitive, very strong, reversible inhibition
barbiturate ribonucleoside 5'-monophosphate
-
very potent inhibitor
phosphate
-
low activity in phosphate buffers, inhibitory or destabilizing effect
pyrazofurin
-
also known as pyrazomycin, potent inhibitor
pyrazofurin-5'-monophosphate
-
slow tight binding inhibitor
additional information
-
inhibitor synthesis, overview
-
additional information
-
not inhibited by 2-thioorotidine 5'-phosphate
-
additional information
-
not inhibited by zinc-chelating agents, e.g. EDTA
-
additional information
-
not inhibited by 6-carboxamidouridine 5’-phosphate, recombinant ODCase expressed in Escherichia coli is not inhibited by 1,3-dimercaptopropanol and EDTA
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoic acid)
-
0.1 mM, at 70°C, 2.2fold 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 70°C, 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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0054
2'-deoxyorotidine 5'-phosphate
-
pH 7.2, 25°C, wild-type enzyme
0.00026
orotidine 5'-phosphate
-
orotidine-5'-phosphate decarboxylase domain of the bifunctional enzyme UMP synthase, 20°C
0.000295
orotidine 5'-phosphate
-
orotidine-5'-phosphate decarboxylase domain of the bifunctional enzyme UMP synthase
0.0006
orotidine 5'-phosphate
-
22-25°C, pH 7.2, recombinant ODCase expressed in Escherichia coli
0.000615
orotidine 5'-phosphate
-
orotidine-5'-phosphate decarboxylase domain of the bifunctional enzyme UMP synthase, 37°C
0.0007
orotidine 5'-phosphate
-
22°C, native ODCase expressed in yeast
0.001 - 0.002
orotidine 5'-phosphate
-
Km value is very dependent on the NaCl concentration, NaCl increases the Km value
0.001
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant I96S, pH 7.1, 25°C
0.0017
orotidine 5'-phosphate
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
0.0018
orotidine 5'-phosphate
-
wild-type, pH 7.1, 25°C
0.0023
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant I96T, pH 7.1, 25°C
0.003
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant L123S, pH 7.1, 25°C
0.0032
orotidine 5'-phosphate
-
multienzyme complex of orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase
0.0035
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant L123N, pH 7.1, 25°C
0.0037
orotidine 5'-phosphate
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
0.0046
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant V155D, pH 7.1, 25°C
0.0047
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant V155S, pH 7.1, 25°C
0.0055
orotidine 5'-phosphate
-
mutant Y206F, pH 7.1, 25°C
0.006
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant D70N, pH 7.1, 25°C
0.0134
orotidine 5'-phosphate
-
monofunctional enzyme expressed in Escherichia coli
0.024
orotidine 5'-phosphate
-
mutant V182A, pH 7.1, 25°C
0.03
orotidine 5'-phosphate
-
mutant R160A, pH 7.1, 25°C
0.033
orotidine 5'-phosphate
-
mutant T159V, pH 7.1, 25°C
0.1 - 1
orotidine 5'-phosphate
-
mutant Q185A, pH 7.1, 25°C
0.1
orotidine 5'-phosphate
-
mutant V182A/Y206F, pH 7.1, 25°C
0.13
orotidine 5'-phosphate
-
mutant R160A/Y206F, pH 7.1, 25°C
0.3
orotidine 5'-phosphate
-
mutant T159V/Y206F, pH 7.1, 25°C
0.6
orotidine 5'-phosphate
-
mutant R160A/V182A, pH 7.1, 25°C
0.7
orotidine 5'-phosphate
-
mutant T159V/V182A, pH 7.1, 25°C
0.98
orotidine 5'-phosphate
-
mutant R203A, pH 7.1, 25°C
1.9
orotidine 5'-phosphate
-
mutant T159V/V182A/Y206F, pH 7.1, 25°C
30
orotidine 5'-phosphate
-
value is higher than 30 mM, pH 7.2, 23°C, mutant enzyme C155S
additional information
additional information
-
kinetic properties, catalytic proficiency/efficiency
-
additional information
additional information
-
kinetic data and mechanism
-
additional information
additional information
-
kinetics, most proficient enzyme known
-
additional information
additional information
-
kinetics and thermodynamics
-
additional information
additional information
-
kinetics
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.15
2'-deoxyorotidine 5'-phosphate
-
pH 7.2, 25°C, wild-type enzyme
92
5-Fluoroorotidine 5'-phosphate
-
mutant R235A, pH 7.1, 25°C, presence of 0.1 M NaCl
95
5-Fluoroorotidine 5'-phosphate
-
wild-type, pH 7.1, 25°C, presence of 0.1 M NaCl
0.0005
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant V155D, pH 7.1, 25°C
0.01 - 1
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant I96S, pH 7.1, 25°C; mutant V155S, pH 7.1, 25°C
0.024
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant D70N, pH 7.1, 25°C
0.24
orotidine 5'-phosphate
-
mutant T159V/V182A/Y206F, pH 7.1, 25°C
0.36
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant L123S, pH 7.1, 25°C
0.56
orotidine 5'-phosphate
-
mutant T159V/V182A, pH 7.1, 25°C
0.64
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant L123N, pH 7.1, 25°C
1
orotidine 5'-phosphate
-
mutant R160A/V182A, pH 7.1, 25°C
1
orotidine 5'-phosphate
-
mutant R235A, pH 7.1, 25°C, presence of 0.1 M NCl
1.1
orotidine 5'-phosphate
-
mutant R160A/Y206F, pH 7.1, 25°C; mutant T159V/Y206F, pH 7.1, 25°C
1.4
orotidine 5'-phosphate
-
mutant Q185A, pH 7.1, 25°C
1.5
orotidine 5'-phosphate
-
mutant R203A, pH 7.1, 25°C; mutant V182A/Y206F, pH 7.1, 25°C
2 - 8
orotidine 5'-phosphate
-
pH 7, constant above pH 7, declines below pH 7
2.3
orotidine 5'-phosphate
-
mutant T159V, pH 7.1, 25°C
4.1
orotidine 5'-phosphate
-
mutant Y206F, pH 7.1, 25°C
7.5
orotidine 5'-phosphate
-
monofunctional enzyme expressed in Escherichia coli
14 - 20
orotidine 5'-phosphate
-
pH 7.2, 25°C, not affected by NaCl concentration
15
orotidine 5'-phosphate
-
wild-type, pH 7.1, 25°C, presence of 0.1 M NaCl
19
orotidine 5'-phosphate
-
22-25°C, pH 7.2, recombinant ODCase expressed in Escherichia coli
24.6
orotidine 5'-phosphate
-
multienzyme complex of orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase
additional information
additional information
-
very high catalytic proficiency
-
additional information
additional information
-
highly proficient enzyme
-
additional information
additional information
-
high catalytic proficiency
-
additional information
additional information
-
50% reduced kcat-value for 4-thioorotidine 5'-phosphate compared with orotidine 5'-phosphate as substrate
-
additional information
additional information
-
remarkable catalytic power
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3
1-(beta-D-erythrofuranosyl)orotic acid
-
mutant Q215A/Y217F/R235A, pH 7.1, 25°C
4.2
1-(beta-D-erythrofuranosyl)orotic acid
-
mutant Q215A/R235A, pH 7.1, 25°C
4.6
1-(beta-D-erythrofuranosyl)orotic acid
-
mutant Q215A/Y217F, pH 7.1, 25°C
10
1-(beta-D-erythrofuranosyl)orotic acid
-
mutant Y217F/R235A, pH 7.1, 25°C
11
1-(beta-D-erythrofuranosyl)orotic acid
-
mutant Q215A, pH 7.1, 25°C
12
1-(beta-D-erythrofuranosyl)orotic acid
-
mutant Y217F, pH 7.1, 25°C
26
1-(beta-D-erythrofuranosyl)orotic acid
-
mutant R235A, pH 7.1, 25°C; wild-type, pH 7.1, 25°C
0.00004
orotidine 5'-phosphate
-
mutant Q215A/Y217F/R235A, pH 7.1, 25°C
0.13
orotidine 5'-phosphate
-
mutant T159V/V182A/Y206F, pH 7.1, 25°C
0.46
orotidine 5'-phosphate
Methanobacterium thermoautotrophicus
-
mutant V155D, pH 7.1, 25°C
0.8
orotidine 5'-phosphate
-
mutant T159V/V182A, pH 7.1, 25°C
1.5
orotidine 5'-phosphate
-
mutant R203A, pH 7.1, 25°C
1.7
orotidine 5'-phosphate
-
mutant R160A/V182A, pH 7.1, 25°C
3.7
orotidine 5'-phosphate
-
mutant T159V/Y206F, pH 7.1, 25°C
8.5
orotidine 5'-phosphate
-
mutant R160A/Y206F, pH 7.1, 25°C
13
orotidine 5'-phosphate
-
mutant Q185A, pH 7.1, 25°C
15
orotidine 5'-phosphate
-
mutant V182A/Y206F, pH 7.1, 25°C
67
orotidine 5'-phosphate
-
mutant R160A, pH 7.1, 25°C
70
orotidine 5'-phosphate
-
mutant T159V, pH 7.1, 25°C
130
orotidine 5'-phosphate
-
mutant V182A, pH 7.1, 25°C
750
orotidine 5'-phosphate
-
mutant Y206F, pH 7.1, 25°C
15000
orotidine 5'-phosphate
-
mutant T80S, pH 7.2, 25°C; wild-type, pH 7.2, 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.022 - 0.028
(5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate
0.00132
6-carbamoyl-UMP
-
in 50 mM Tris, pH 7.5, 20 mM dithiothreitol, and 40 mM NaCl, at 55°C
0.0000035
6-thiocarboxamidouridine 5'-phosphate
-
recombinant ODCase expressed in Escherichia coli
0.000000009
barbiturate ribonucleoside 5'-monophosphate
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
0.022
(5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate
pH 7.5, 22°C
0.028
(5-(4-amino-3-oxido-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl)-methyl dihydrogen phosphate
-
pH 7.5, 22°C
0.36
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
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
9.1
5-cyano-UMP
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
290
5-cyano-UMP
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
550
5-cyano-UMP
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
3.322
6-amido-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
0.037
6-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
2
6-cyano-2'-deoxy-2'-fluoro-beta-D-uridine 5'-O-monophosphate
-
Ki above 2 mM, in 50 mM Tris, pH 7.5, 20 mM dithiothreitol, and 40 mM NaCl, at 55°C
0.0286
6-cyanouridine
-
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
0.000005
pyrazofurin-5'-monophosphate
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
0.000017
pyrazofurin-5'-monophosphate
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
0.00013
pyrazofurin-5'-monophosphate
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
0.0062
pyrazofurin-5'-monophosphate
-
in 50 mM Tris (pH 7.5), 20 mM dithiothreitol, and 40 mM NaCl, at 22°C
additional information
additional information
-
inhibition kinetics
-
additional information
additional information
-
inhibition kinetics, isothermal calorimetry
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0044 - 0.0062
6-iodo-UMP
Plasmodium falciparum
-
pH 7.5, 22°C, with different Plasmodium falciparum isolates
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE