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Information on EC 4.1.1.23 - orotidine-5'-phosphate decarboxylase
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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
-
phosphoribosyl
- 6-azauridine
- pyrazofurin
-
2.4.2.10
-
aciduria
-
transcarbamoylase
-
carbanions
- oprtase
- phosphite
- 5-fluorouridine
-
pyre
-
decarboxylases
-
phosphodianion
- dianion
-
barbituric
-
prototrophy
- biotechnology
- pharmacology
- medicine
- molecular biology
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
odcase, ump synthase, orotidine 5'-monophosphate decarboxylase, omp decarboxylase, orotidine-5'-monophosphate decarboxylase, ompdc, orotidine monophosphate decarboxylase, orotidylate decarboxylase, orotidine 5'-phosphate decarboxylase, ompdecase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Decarboxylase, orotidine 5'-phosphate
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ODCase
OMP decarboxylase
OMP-DC
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OMPD
OMPDC
OMPDCase
OMPdecase
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Orotate decarboxylase
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Orotate monophosphate decarboxylase
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Orotic decarboxylase
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Orotidine 5'-monophosphate decarboxylase
Orotidine 5'-phosphate decarboxylase
orotidine 5-monophosphate decarboxylase
Orotidine monophosphate decarboxylase
Orotidine phosphate decarboxylase
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Orotidine-5'-monophosphate decarboxylase
orotidine-5'-phosphate decarboxylase
orotidine-5-monophosphate decarboxylase
Orotidylate decarboxylase
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Orotidylic acid decarboxylase
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Orotidylic decarboxylase
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Orotodylate decarboxylase
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pm-ura3
PyrF
ScOMPDC
UMP synthase
URA3
Uridine 5'-monophosphate synthase
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ODCase
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ODCase
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OMP decarboxylase
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OMPDCase
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Orotidine 5'-monophosphate decarboxylase
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Orotidine 5'-monophosphate decarboxylase
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Orotidine 5'-monophosphate decarboxylase
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Orotidine 5'-monophosphate decarboxylase
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Orotidine 5'-phosphate decarboxylase
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Orotidine monophosphate decarboxylase
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Orotidine-5'-monophosphate decarboxylase
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UMP synthase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
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orotidine 5'-phosphate = UMP + CO2
mechanism, thermodynamic data
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orotidine 5'-phosphate = UMP + CO2
mechanism
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orotidine 5'-phosphate = UMP + CO2
catalytic mechanism
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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
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orotidine 5'-phosphate = UMP + CO2
direct decarboxylation mechanism, modeling with 6-carbanion derivatives of uracil analogues, overview
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orotidine 5'-phosphate = UMP + CO2
catalysis by OMPDC is due to stabilization of the decarboxylation transition state by interactions with the protein catalyst leading to a 1023-fold rate acceleration. The falloff in the second-order rate constants for OMPDC-catalyzed decarboxylation observed upon the truncation of the phosphodianion and the ribosyl phosphate from the substrate orotidine 5'-phosphate (OMP), catalytic mechanism, detailed overview. Interaction between the side chains of Ser154 and Gln215 wild-type ScOMPDC is required to hold the amide side chain in a position to interact with the substrate phosphodianion. The dianion binding interactions with Gln215, Tyr217, and Arg235 serve the exclusive function of activating OMPDC for catalysis at the pyrimidine binding site
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orotidine 5'-phosphate = UMP + CO2
catalysis by OMPDC is due to stabilization of the decarboxylation transition state by interactions with the protein catalyst leading to a 1023-fold rate acceleration. The falloff in the second-order rate constants for OMPDC-catalyzed decarboxylation observed upon the truncation of the phosphodianion and the ribosyl phosphate from the substrate orotidine 5'-phosphate (OMP), catalytic mechanism, detailed overview. Interaction between the side chains of Ser154 and Gln215 wild-type ScOMPDC is required to hold the amide side chain in a position to interact with the substrate phosphodianion. The dianion binding interactions with Gln215, Tyr217, and Arg235 serve the exclusive function of activating OMPDC for catalysis at the pyrimidine binding site
Saccharomyces cerevisiae ATCC 204508 / S288c
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orotidine 5'-phosphate = UMP + CO2
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decarboxylation
decarboxylation
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PATHWAY SOURCE
PATHWAYS
BRENDA
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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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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
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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
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truncated substrate
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-
?
5'-deoxy-5-fluoroorotidine
? + CO2
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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
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-
?
6-cyano-UMP
6-hydroxyuridine 5'-phosphate + UMP
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-
-
-
?
1-(beta-D-erythrofuranosyl)-5-fluoroorotate
1-(beta-D-erythrofuranosyl)-5-fluorouracil + CO2
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-
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1-(beta-D-erythrofuranosyl)-5-fluoroorotate
1-(beta-D-erythrofuranosyl)-5-fluorouracil + CO2
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-
-
-
?
1-(beta-D-erythrofuranosyl)-5-fluoroorotate
1-(beta-D-erythrofuranosyl)-5-fluorouracil + CO2
Saccharomyces cerevisiae ATCC 204508 / S288c
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1-(beta-D-erythrofuranosyl)-5-fluoroorotate
1-(beta-D-erythrofuranosyl)-5-fluorouracil + CO2
Saccharomyces cerevisiae ATCC 204508 / S288c
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1-(beta-D-erythrofuranosyl)-5-fluoroorotate
1-(beta-D-erythrofuranosyl)-5-fluorouracil + CO2
Saccharomyces cerevisiae ATCC 204508 / S288c
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?
1-(beta-D-erythrofuranosyl)-orotate
1-(beta-D-erythrofuranosyl)uracil + CO2
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?
1-(beta-D-erythrofuranosyl)-orotate
1-(beta-D-erythrofuranosyl)uracil + CO2
Saccharomyces cerevisiae ATCC 204508 / S288c
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?
1-(beta-D-erythrofuranosyl)-orotate
1-(beta-D-erythrofuranosyl)uracil + CO2
Saccharomyces cerevisiae ATCC 204508 / S288c
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?
2'-deoxyorotidine 5'-phosphate
2'-deoxyuridine 5'-phosphate + CO2
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decreased catalytic rate compared with orotidine 5'-phosphate as substrate
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?
2'-deoxyorotidine 5'-phosphate
2'-deoxyuridine 5'-phosphate + CO2
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-
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?
2'-deoxyorotidine 5'-phosphate
2'-deoxyuridine 5'-phosphate + CO2
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?
2'-deoxyorotidine 5'-phosphate
2'-deoxyuridine 5'-phosphate + CO2
less effective than orotidine 5’-phosphate
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?
4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
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partially active substrate
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?
4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
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50% reduced kcat-value compared with orotidine 5'-phosphate as substrate
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?
4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
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4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
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nearly equally effective as orotidine 5'-phosphate
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?
4-Thioorotidine 5'-phosphate
4-Thiouridine 5'-phosphate + CO2
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nearly equally effective as orotidine 5'-phosphate
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?
5-fluoroorotidine 5'-phosphate
5-fluoro-UMP + CO2
Saccharomyces cerevisiae ATCC 204508 / S288c
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?
5-Fluoroorotidine 5'-phosphate
5-Fluorouridine 5'-phosphate + CO2
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5-Fluoroorotidine 5'-phosphate
5-Fluorouridine 5'-phosphate + CO2
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?
5-Fluoroorotidine 5'-phosphate
5-Fluorouridine 5'-phosphate + CO2
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?
5-Fluoroorotidine 5'-phosphate
5-Fluorouridine 5'-phosphate + CO2
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the 5-fluoro substituent results in a 3400fold increase in the first-order rate constant for deuterium exchange
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?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
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pseudohydrolysis process
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?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
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?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
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pseudohydrolysis process
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?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
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pseudohydrolysis process
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?
6-cyanouridine 5'-monophosphate
6-hydroxyuridine 5'-monophosphate + CN-
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pseudohydrolysis process
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?
Orotidine 5'-phosphate
?
-
final step in pyrimidine biosynthesis
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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
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?
Orotidine 5'-phosphate
UMP + CO2
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mechansim, no formation of a vinyl anion intermediate, enzyme structure, the active sites are located at the dimer interface
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?
Orotidine 5'-phosphate
UMP + CO2
catalyzes the final step in the de novo biosynthesis of uridine monophosphate
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?
Orotidine 5'-phosphate
UMP + CO2
last common step in pyrimidine biosynthesis, constitutive expression
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?
Orotidine 5'-phosphate
UMP + CO2
last common step in pyrimidine biosynthesis, constitutive expression
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?
Orotidine 5'-phosphate
UMP + CO2
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catalytic mechanism, role of Lys-93 in catalysis, enzyme structure
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?
Orotidine 5'-phosphate
UMP + CO2
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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
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?
Orotidine 5'-phosphate
UMP + CO2
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catalyzes the last step in the de novo synthesis of UMP
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?
Orotidine 5'-phosphate
UMP + CO2
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last step in the de novo synthesis of pyrimidine nucleotides
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?
Orotidine 5'-phosphate
UMP + CO2
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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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?
Orotidine 5'-phosphate
UMP + CO2
Methanobacterium thermoautotrophicus DSM 1053
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?
Orotidine 5'-phosphate
UMP + CO2
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?
Orotidine 5'-phosphate
UMP + CO2
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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
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?
Orotidine 5'-phosphate
UMP + CO2
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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
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?
Orotidine 5'-phosphate
UMP + CO2
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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
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?
Orotidine 5'-phosphate
UMP + CO2
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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
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?
Orotidine 5'-phosphate
UMP + CO2
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catalyzes the final step in the de novo biosynthesis of UMP
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?
Orotidine 5'-phosphate
UMP + CO2
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catalyzes the last step of de novo pyrimidine synthesis
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?
Orotidine 5'-phosphate
UMP + CO2
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last step in the biosynthesis of pyrimidine nucleotides
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?
Orotidine 5'-phosphate
UMP + CO2
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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
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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
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-
?
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
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?
Orotidine 5'-phosphate
UMP + CO2
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-
-
-
?
Orotidine 5'-phosphate
UMP + CO2
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the sixth enzyme in the pathway catalyzing formation of uridine 5'-monophosphate
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?
Orotidine 5'-phosphate
UMP + CO2
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final step in the de novo synthesis of uridine 5'-monophosphate, UMP, defects in the enzyme are lethal in the malaria parasite
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-
?
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
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-
?
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
-
-
661317, 678241, 682233, 690984, 690986, 692757, 694055, 714449, 726986, 727033, 727673, 746572, 747089, 748024, 748039
-
-
?
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
-
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
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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
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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
?
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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
-
-
-
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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
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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INHIBITOR
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
hydroxyuridine 5'-monophosphate
-
strong binding of 6-hydroxyuridine 5'-monophosphate (BMP) to OMPDC induces a protein conformational change. This includes closure of the phosphodianion gripper loop (Pro202-Val220) and pyrimidine umbrella (Glu152-Thr165) over the inhibitor, which locks BMP in a protein cage. Interactions of the ligand phosphodianion with the amide side chain of Gln215, the phenol side chain of Tyr217, the guanidine side chain of Arg235, which sits on the protein surface adjacent to the gripper loop and functions cooperatively with the loop side chains in activating OMPDC for catalysis, and with backbone amides from Gly234 and Arg235
-
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
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoic acid)
-
0.1 mM, at 70°C, 2.2fold activation
D-erythritol 4-phosphate
-
activates the decarboxylation of 5-fluoroorotate. This activation is due to the utilization of binding energy from interactions between OMPDC and activator
D-glycerol 3-phosphate
-
activates the decarboxylation of 5-fluoroorotate.
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
additional information
-
enzyme ScOMPDC-catalyzed decarboxylation of 5-fluoroorotate is stabilized by 5.2, 7.2, and 9.0 kcal/mol, respectively, by 1.0 M phosphite dianion, D-glycerol 3-phosphate and D-erythritol 4-phosphate, so that binding interactions between both the substrate phosphodianion and the ribosyl hydroxyls are utilized to activate ScOMPDC for catalysis
-
phosphite dianion
-
strong phosphite dianion activation of ScOMPDC-catalyzed decarboxylation of of 1-(beta-D-erythrofuranosyl)-5-fluoroorotate (FEO), of 5-fluoroorotate (FO) and of 1-(beta-D-erythrofuranosyl)-orotic acid. Utilization of intrinsic dianion energy
phosphite dianion
-
the activation with substrate 1-(beta-D-erythrofuranosyl)-orotate is due to the utilization of binding energy from interactions between OMPDC and activator to drive a complex conformational change from inactive open OMPDC (EO) to the active closed caged complex (EC), where EC is stabilized relative to EO by interactions between dianions and the side chains of Q215, Y217, and R235
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Anemia, Hypoplastic, Congenital
Elevation of pyrimidine enzyme activities in the RBC of patients with congenital hypoplastic anaemia and their parents.
Candidiasis
Evaluation of the roles of four Candida albicans genes in virulence by using gene disruption strains that express URA3 from the native locus.
Carcinoma
Isolation and initial characterization of the single polypeptide that synthesizes uridine 5'-monophosphate from orotate in Ehrlich ascites carcinoma. Purification by tandem affinity chromatography of uridine-5'-monophosphate synthase.
Carcinoma
Potential for ambiguity in the interpretation of immunochemical studies on multienzymic proteins. The case of uridylate synthase.
Carcinoma
Purification, size, and properties of the complex of orotate phosphoribosyltransferase: orotidylate decarboxylase from mouse Ehrlich ascites carcinoma.
Carcinoma
The purification and preliminary characterization of UMP synthase from human placenta.
Carcinoma, Hepatocellular
Amplification of the UMP synthase gene and enzyme overproduction in pyrazofurin-resistant rat hepatoma cells. Molecular cloning of a cDNA for UMP synthase.
Carcinoma, Hepatocellular
Increased levels of UMP synthase protein and mRNA in pyrazofurin-resistant rat hepatoma cells.
Carcinoma, Hepatocellular
Orotate phosphoribosyl transferase and orotidylic acid decarboxylase activities in liver and Morris hepatomas.
Carcinoma, Hepatocellular
Potentiation of antimetabolite action by dibromodulcitol in cell culture.
Communicable Diseases
Design of inhibitors of orotidine monophosphate decarboxylase using bioisosteric replacement and determination of inhibition kinetics.
Communicable Diseases
Inhibition of orotidine 5'-monophosphate decarboxylase and its therapeutic potential.
Cysts
Nonreplicating, cyst-defective type II Toxoplasma gondii vaccine strains stimulate protective immunity against acute and chronic infection.
Hepatitis B
Another ten stories in antiviral drug discovery (part C): "Old" and "new" antivirals, strategies, and perspectives.
Herpes Simplex
Another ten stories in antiviral drug discovery (part C): "Old" and "new" antivirals, strategies, and perspectives.
HIV Infections
Another ten stories in antiviral drug discovery (part C): "Old" and "new" antivirals, strategies, and perspectives.
Infection
Another ten stories in antiviral drug discovery (part C): "Old" and "new" antivirals, strategies, and perspectives.
Infection
Nonreplicating, cyst-defective type II Toxoplasma gondii vaccine strains stimulate protective immunity against acute and chronic infection.
Leukemia
Studies on a pyrimidine phosphoribosyltransferase from murine leukemia P1534J. Partial purification, substrate specificity, and evidence for its existence as a bifunctional complex with orotidine 5-phosphate decarboxylase.
Lymphoma
Pyrimidine pathway variants of cultured mouse lymphoma cells with altered levels of both orotate phosphoribosyltransferase and orotidylate decarboxylase.
Malaria
A novel enzyme complex of orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase in human malaria parasite Plasmodium falciparum: physical association, kinetics, and inhibition characterization.
Malaria
A potent, covalent inhibitor of orotidine 5'-monophosphate decarboxylase with antimalarial activity.
Malaria
A unique insertion of low complexity amino acid sequence underlies protein-protein interaction in human malaria parasite orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase.
Malaria
Crystallization and preliminary crystallographic analysis of orotidine 5'-monophosphate decarboxylase from the human malaria parasite Plasmodium falciparum.
Malaria
Inhibition of orotidine 5'-monophosphate decarboxylase and its therapeutic potential.
Malaria
Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target.
Malaria
Kinetic benefits and thermal stability of orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase enzyme complex in human malaria parasite Plasmodium falciparum.
Malaria
Novel cytidine-based orotidine-5'-monophosphate decarboxylase inhibitors with an unusual twist.
Malaria
Orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase exist as multienzyme complex in human malaria parasite Plasmodium falciparum.
Neoplasms
Enzymes of the de novo and salvage pathways for pyrimidine biosynthesis in normal colon, colon carcinoma, and xenografts.
Neoplasms
Inhibition of orotidine 5'-monophosphate decarboxylase and its therapeutic potential.
Neoplasms
Structures of the human orotidine-5'-monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design.
ornithine carbamoyltransferase deficiency
Activity of orotate metabolizing enzyme complex and various urea-cycle enzymes in mutant mice with ornithine transcarbamylase deficiency.
Ornithine Carbamoyltransferase Deficiency Disease
Activity of orotate metabolizing enzyme complex and various urea-cycle enzymes in mutant mice with ornithine transcarbamylase deficiency.
orotidine-5'-phosphate decarboxylase deficiency
Consequences of UMP synthase deficiency in cattle.
orotidine-5'-phosphate decarboxylase deficiency
Deficiency of UMP synthase in dairy cattle: a model for hereditary orotic aciduria.
orotidine-5'-phosphate decarboxylase deficiency
Detection and prevalence of UMP synthase deficiency among dairy cattle.
orotidine-5'-phosphate decarboxylase deficiency
Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families.
pantoate-beta-alanine ligase (amp-forming) deficiency
Disorders of purine and pyrimidine metabolism.
Parasitic Diseases
Inhibition of orotidine 5'-monophosphate decarboxylase and its therapeutic potential.
Poxviridae Infections
Therapy and short-term prophylaxis of poxvirus infections: historical background and perspectives.
Sarcoma, Avian
Activation of ornithine decarboxylase in monolayer cells treated with trypsin.
Smallpox
Therapy and short-term prophylaxis of poxvirus infections: historical background and perspectives.
Starvation
Effects of phosphate limitation on expression of genes involved in pyrimidine synthesis and salvaging in Arabidopsis.
Tuberculosis
Validation of CoaBC as a Bactericidal Target in the Coenzyme A Pathway of Mycobacterium tuberculosis.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0054
2'-deoxyorotidine 5'-phosphate
-
pH 7.2, 25°C, wild-type enzyme
0.008
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, wild-type enzyme
0.086
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant S154A/Q215A
0.65
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/R235A
0.92
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/Y271F
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
0.002
orotidine 5'-phosphate
-
pH and temperature not specified in the publication, recombinant bifunctional enzyme, OMPDC activity
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
0.0105
orotidine 5'-phosphate
-
pH and temperature not specified in the publication, recombinant multienzyme complex, OMPDC activity
0.0134
orotidine 5'-phosphate
-
monofunctional enzyme expressed in Escherichia coli
0.0134
orotidine 5'-phosphate
-
pH and temperature not specified in the publication, recombinant monofunctional enzyme, OMPDC activity
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
0.11
orotidine 5'-phosphate
-
pH 7.1, 25°C, mutant R235A; pH 7.1, 25°C, mutant Y217F
0.13
orotidine 5'-phosphate
-
mutant R160A/Y206F, pH 7.1, 25°C
0.29 - 1.4
orotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/Y271F
0.3
orotidine 5'-phosphate
-
mutant T159V/Y206F, pH 7.1, 25°C
0.35 - 1.4
orotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/R235A
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
2.2 - 12.9
orotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/Y217F/R235A
6.1 - 27.1
orotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Y217F/R235A
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
-
additional information
additional information
-
kinetic analysis of wild-type and mutant enzymes with substrates orotidine 5'-phosphate and 5-fluoroorotidine 5'-phosphate, rate and equilibrium constants for the conformational change that traps 5-fluoroorotidine 5'-phosphate at the enzyme active site
-
additional information
additional information
-
kinetic analysis of wild-type and mutant enzymes with substrate orotidine 5'-phosphate
-
additional information
additional information
-
substrate specificity and kinetic analysis, overview
-
additional information
additional information
-
Michaelis-Menten kinetics
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.15
2'-deoxyorotidine 5'-phosphate
-
pH 7.2, 25°C, wild-type enzyme
4.7
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/R235A
6.6
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant S154A/Q215A
49
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/Y271F
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
0.00048
orotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/Y217F/R235A
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
0.19 - 0.2
orotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/R235A
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
7.5
orotidine 5'-phosphate
-
pH and temperature not specified in the publication, recombinant monofunctional enzyme, OMPDC activity
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
30.7
orotidine 5'-phosphate
-
pH and temperature not specified in the publication, recombinant multienzyme complex, OMPDC activity
985.8
orotidine 5'-phosphate
-
pH and temperature not specified in the publication, recombinant bifunctional enzyme, OMPDC activity
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
0.00002
1-(beta-D-erythrofuranosyl)-orotate
-
pH 7.0, 25°C, wild-type enzyme
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
0.028
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/Y217F/R235A
0.82
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Y217F/R235A
7.23
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/R235A
53.3
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/Y271F
76.7
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, mutant S154A/Q215A
11875
5-Fluoroorotidine 5'-phosphate
-
pH 7.1, 25°C, wild-type enzyme
0.000037 - 0.00022
orotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/Y217F/R235A
0.00004
orotidine 5'-phosphate
-
mutant Q215A/Y217F/R235A, pH 7.1, 25°C
0.0041 - 0.018
orotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Y217F/R235A
0.014 - 0.054
orotidine 5'-phosphate
-
pH 7.1, 25°C, mutant Q215A/R235A
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
559.7
orotidine 5'-phosphate
-
pH and temperature not specified in the publication, recombinant monofunctional enzyme, OMPDC activity
750
orotidine 5'-phosphate
-
mutant Y206F, pH 7.1, 25°C
2923.8
orotidine 5'-phosphate
-
pH and temperature not specified in the publication, recombinant multienzyme complex, OMPDC activity
15000
orotidine 5'-phosphate
-
mutant T80S, pH 7.2, 25°C; wild-type, pH 7.2, 25°C
492900
orotidine 5'-phosphate
-
pH and temperature not specified in the publication, recombinant bifunctional enzyme, OMPDC activity
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
0.015
4-thiouridine 5'-phosphate