4.1.1.23: orotidine-5'-phosphate decarboxylase
This is an abbreviated version!
For detailed information about orotidine-5'-phosphate decarboxylase, go to the full flat file.
Word Map on EC 4.1.1.23
-
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
- 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
Reaction
Synonyms
Decarboxylase, orotidine 5'-phosphate, More, ODCase, OMP decarboxylase, OMP-DC, OMPD, OMPDC, OMPDCase, OMPdecase, Orotate decarboxylase, Orotate monophosphate decarboxylase, Orotic decarboxylase, Orotidine 5'-monophosphate decarboxylase, Orotidine 5'-phosphate decarboxylase, orotidine 5-monophosphate decarboxylase, orotidine 5-phosphate decarboxylase, Orotidine monophosphate decarboxylase, Orotidine phosphate decarboxylase, Orotidine-5'-monophosphate decarboxylase, orotidine-5'-phosphate decarboxylase, orotidine-5-monophosphate decarboxylase, Orotidylate decarboxylase, Orotidylic acid decarboxylase, Orotidylic decarboxylase, Orotodylate decarboxylase, PbrURA3, PfODCase, PfOMPDC, pm-ura3, PyrF, ScOMPDC, UMP synthase, URA3, Uridine 5'-monophosphate synthase
ECTree
4.1.1.23 orotidine-5'-phosphate decarboxylaseAdvanced search results
results (
results (Substrates Products
Substrates Products on EC 4.1.1.23 - orotidine-5'-phosphate decarboxylase
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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-fluoroorotate
1-(beta-D-erythrofuranosyl)-5-fluorouracil + CO2
1-(beta-D-erythrofuranosyl)-5-fluoroorotic acid
1-(beta-D-erythrofuranosyl)-5-fluorouracil + 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
1-(beta-D-erythrofuranosyl)uracil + CO2
-
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 + H2O
barbiturate ribonucleoside 5'-monophosphate + CN-
-
-
-
-
?
6-cyano-UMP + H2O
beta-D-ribofuranosylbarbiturate 5'-monophosphate + CN-
-
hydrolysis
-
-
?
1-(beta-D-erythrofuranosyl)-5-fluoroorotate
1-(beta-D-erythrofuranosyl)-5-fluorouracil + CO2
-
-
-
?
1-(beta-D-erythrofuranosyl)-5-fluoroorotate
1-(beta-D-erythrofuranosyl)-5-fluorouracil + CO2
Saccharomyces cerevisiae ATCC 204508 / S288c
-
-
-
?
1-(beta-D-erythrofuranosyl)-orotate
1-(beta-D-erythrofuranosyl)uracil + CO2
-
-
-
?
1-(beta-D-erythrofuranosyl)-orotate
1-(beta-D-erythrofuranosyl)uracil + CO2
Saccharomyces cerevisiae ATCC 204508 / S288c
-
-
-
?
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-fluoro-UMP + CO2
Saccharomyces cerevisiae ATCC 204508 / S288c
-
-
-
?
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
-
-
-
?
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
-
-
-
?
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 substrates 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
stepwise mechanism via a UMP carbanion intermediate, modeling of the transition state stabilization
-
-
?
Orotidine 5'-phosphate
UMP + CO2
Saccharomyces cerevisiae ATCC 204508 / S288c
stepwise mechanism via a UMP carbanion intermediate, modeling of the transition state stabilization
-
-
?
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
?
-
extraordinary specificity of OMPDC in binding the decarboxylation transition state with a higher affinity compared with the substrate orotidine 5'-phosphate. Substrate specificity and kinetic analysis, structure-function analysis, detailed overview
-
-
?
additional information
?
-
ScOMPDC also catalyzes decarboxylation of 1-(beta-D-erythrofuranosyl)-5-fluoroorotate (FEO), of 5-fluoroorotate (FO), and of 1-(beta-D-erythrofuranosyl)-orotic acid (EO). Open and the closed forms of enzyme ScOMPDC: phosphodianion gripper loop (with structural heterogeneity between organisms) and pyrimidine umbrella, structure, overview. Reaction mechanism and kinetics with different substrates, transition state analysis
-
-
?
additional information
?
-
two flexible loops close to form the active site cage: Pro202-Val220, on the left-hand side of each structure, interact with the substrate dianion, and Glu152-Thr165, on the right-hand side, interact with the pyrimidine ring. The tyrosyl phenol group stabilizes the closed form of ScOMPDC by hydrogen bonding to the substrate phosphodianion, and that the phenyl group of Y217 and F217 facilitates formation of the transition state for the rate-limiting conformational change
-
-
?
additional information
?
-
Saccharomyces cerevisiae ATCC 204508 / S288c
ScOMPDC also catalyzes decarboxylation of 1-(beta-D-erythrofuranosyl)-5-fluoroorotate (FEO), of 5-fluoroorotate (FO), and of 1-(beta-D-erythrofuranosyl)-orotic acid (EO). Open and the closed forms of enzyme ScOMPDC: phosphodianion gripper loop (with structural heterogeneity between organisms) and pyrimidine umbrella, structure, overview. Reaction mechanism and kinetics with different substrates, transition state analysis
-
-
?
additional information
?
-
Saccharomyces cerevisiae ATCC 204508 / S288c
two flexible loops close to form the active site cage: Pro202-Val220, on the left-hand side of each structure, interact with the substrate dianion, and Glu152-Thr165, on the right-hand side, interact with the pyrimidine ring. The tyrosyl phenol group stabilizes the closed form of ScOMPDC by hydrogen bonding to the substrate phosphodianion, and that the phenyl group of Y217 and F217 facilitates formation of the transition state for the rate-limiting conformational change
-
-
?
additional information
?
-
Saccharomyces cerevisiae ATCC 204508 / S288c
extraordinary specificity of OMPDC in binding the decarboxylation transition state with a higher affinity compared with the substrate orotidine 5'-phosphate. Substrate specificity and kinetic analysis, structure-function analysis, detailed overview
-
-
?
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
-
-
?
