Information on EC 2.4.2.10 - orotate phosphoribosyltransferase

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

EC NUMBER
COMMENTARY
2.4.2.10
-
RECOMMENDED NAME
GeneOntology No.
orotate phosphoribosyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
mechanism
-
orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
mechanism is bi bi ping pong
-
orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
mechanism
-
orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
ping pong mechanism is not operable, NMR exchange experiments
-
orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
random sequential kinetic mechanism
Q8N0R1
orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
reaction scheme, half-of-sites binding of orotidine 5-phosphate and alpha-D-5-phosphorylribose 1-diphosphate to the enzyme supports an alternative variant of the Theorell-Chance mechanism with alternating site catalysis, in addition to a ping-pong bi-bi kinetic mechanism, overview
-
orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pentosyl group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Drug metabolism - other enzymes
-
Metabolic pathways
-
Pyrimidine metabolism
-
UMP biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
orotidine-5'-phosphate:diphosphate phospho-alpha-D-ribosyl-transferase
The enzyme from higher eukaryotes also catalyses the reaction listed as EC 4.1.1.23, orotidine-5'-phosphate decarboxylase.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
OMP synthase
-
-
OPRT
-
-
-
-
OPRTase
-
-
-
-
OPRTase
P13298
-
OPRTase
Q8DTV2
-
orotate phosphoribosyl pyrophosphate transferase
-
-
-
-
orotate phosphoribosyl transferase
-
-
orotate phosphoribosyltransferase
-
-
-
-
orotate phosphoribosyltransferase
-
-
orotate phosphoribosyltransferase
-
-
orotate phosphoribosyltransferase
L0T6H8
-
orotate phosphoribosyltransferase
-
-
orotate phosphoribosyltransferase
-
-
orotate phosphoribosyltransferase
Q8DTV2
-
orotate PRTase
-
-
-
-
orotic acid phosphoribosyltransferase
-
-
-
-
orotidine 5'-monophosphate pyrophosphorylase
-
-
-
-
orotidine 5'-monophosphate pyrophosphorylase
-
-
orotidine 5'-phosphate pyrophosphorylase
-
-
-
-
orotidine monophosphate pyrophosphorylase
-
-
-
-
orotidine phosphoribosyltransferase
-
-
-
-
orotidine-5'-phosphate pyrophosphorylase
-
-
-
-
orotidylate phosphoribosyltransferase
-
-
-
-
orotidylate pyrophosphorylase
-
-
-
-
orotidylic acid phosphorylase
-
-
-
-
orotidylic acid pyrophosphorylase
-
-
-
-
orotidylic phosphorylase
-
-
-
-
orotidylic pyrophosphorylase
-
-
-
-
phosphoribosyltransferase, orotate
-
-
-
-
type I phosphoribosyltransferase
-
-
ura5
Mortierella alpina 1S-4
-
-
-
additional information
-
enzyme from mammals is a bifunctional polypeptide, it also catalyzes the reaction listed as EC 4.1.1.23
additional information
-
constitutes together with orotidylate decarboxylase (EC 4.1.1.23) UMP-synthase, former complex U or multienzyme pyr-5,6
additional information
-
enzyme from mammals is a bifunctional polypeptide, it also catalyzes the reaction listed as EC 4.1.1.23
additional information
-
-
additional information
Plasmodium falciparum FCB
-
-
-
additional information
-
enzyme from mammals is a bifunctional polypeptide, it also catalyzes the reaction listed as EC 4.1.1.23
CAS REGISTRY NUMBER
COMMENTARY
9030-25-5
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain ATCC 6872
-
-
Manually annotated by BRENDA team
K-12, overproducing strains C-600(pNE24) (wild-type) and its purine-sensitive mutant PS100(pNE31), both harbouring hybrid multi-copy plasmids
-
-
Manually annotated by BRENDA team
patients with bladder carcinoma
-
-
Manually annotated by BRENDA team
strain 1S-4
-
-
Manually annotated by BRENDA team
Mortierella alpina 1S-4
strain 1S-4
-
-
Manually annotated by BRENDA team
FCB strain
-
-
Manually annotated by BRENDA team
multienzyme complex together with orotidine 5-monophosphate decarboxylase
-
-
Manually annotated by BRENDA team
Plasmodium falciparum FCB
FCB strain
-
-
Manually annotated by BRENDA team
strain ATCC 17536. When grown on glucose as carbon source, supplementation with orotic acid significantly decreases orotate phosphoribosyltransferase and orotidine 5'-monophoshate decarboxylase activities. In a strain deficient for dihydroorotase activity, orotic acid induces both phosphoribosyltransferase and orotidine 5'-monophoshate decarboxylase activites
-
-
Manually annotated by BRENDA team
biovar trifolium
-
-
Manually annotated by BRENDA team
structural gene pyrE cloned and overexpressed via multi-copy plasmid in Escherichia coli strain MB13
-
-
Manually annotated by BRENDA team
recombinant enzyme
-
-
Manually annotated by BRENDA team
black gram
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
decreased activity of OPRT plays an important role in the acquired resistance of gastric cancer cells towards 5-fluorouracil. OPRT-knockout MKN-45 parent cells using small interfering RNA demonstrate 15.8fold increased resistance to 5-fluorouracil compared to the control cell
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5-fluoroorotate + 5-phospho-alpha-D-ribose 1-diphosphate
?
show the reaction diagram
Q8N0R1
-
-
-
?
5-fluoroorotate + phosphoribose diphosphate
5-fluoroorotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
?
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
?
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
essential enzyme for activation of 5-fluorouracil and its derivatives
-
-
?
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
the activating OPRT and its antagonist the catabolizing dihydropyrimidine dehydrogenase play important roles in 5-fluorouracil metabolism, overview
-
-
?
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
the enzyme is involved in degradation of 5-fluorouracil being the key enzyme related to the first-step activation process of 5-fluorouracil, and possibly predicts chemosensitivity to 5-fluorouracil, overview
-
-
?
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
the enzyme is involved in the de novo biosynthesis of pyrimidine nucleotides, main enzyme involved in phosphoribosylation of 5-fluorouracil, an essential step that leads to tumor growth inhibition
-
-
?
orotate + 5-alpha-D-phosphorylribose 1-diphosphate
diphosphate + orotidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
-
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
-
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
-
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
r
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
r
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
r
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
r
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
Q8T6J6
-
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
Q8N0R1
-
-
-
r
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
P13298
-
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
L0T6H8, -
-
-
-
r
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
-
i.e. orotidylate or OMP
-
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
catalyzes stereospecific formation of beta-glycosidic bond between orotate and ribose 5'-phosphate portion of phospho-ribose diphosphate, predominant species of phosphoribose diphosphate: metal ion complex
-
r
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
reverse reaction: tri-, tetrapoly- or trimetaphosphate can replace diphosphate with 29%, 70% or 78% efficiency
-
-
r
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
high specificity for orotate
-
r
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
nucleotide-forming step in pyrimidine biosynthesis
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
final steps in biosynthesis of UMP
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
involved in de novo synthesis of pyrimidine nucleotides
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
involved in de novo synthesis of pyrimidine nucleotides
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
Plasmodium falciparum FCB
-
-, final steps in biosynthesis of UMP
-
-
?
orotate methylester + phosphoribose diphosphate
diphosphate + orotidine 4-methylester
show the reaction diagram
-
-
-
-
?
orotidine + diphosphate
orotate + alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
?
orotidine + diphosphate
orotate + alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
r
orotidine + diphosphate
orotate + alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
?
orotidine + diphosphate
orotate + alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
r
orotidine 5'-phosphate + diphosphate
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
?
orotidine 5'-phosphate + diphosphate
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
r
orotidine 5'-phosphate + diphosphate
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
?
orotidine 5'-phosphate + diphosphate
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
r
orotidine 5'-phosphate + diphosphate
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
L0T6H8, -
-
-
-
r
orotidine 5'-phosphate + phosphonoacetic acid
?
show the reaction diagram
-
-
-
-
?
orotidine 5-phosphate + diphosphate
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
?
orotidine 5-phosphate + diphosphate
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
the compounds bind very tightly to the enzyme in a Mg2+-dependent manner, overview
the compounds bind very tightly to the enzyme in a Mg2+-dependent manner, overview
-
?
uracil + phosphoribose diphosphate
diphosphate + uridine
show the reaction diagram
-
-
-
-
?
uracil + phosphoribose diphosphate
diphosphate + uridine
show the reaction diagram
-
not substrate
-
-
-
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
the enzyme is involved in the metabolism of 5-fluorouracil, a chemotherapeutic drug in treatment of solid cancers, major pathways of 5-fluorouracil metabolism, overview
-
-
?
additional information
?
-
-
enzyme from mammals is a bifunctional polypeptide, it also catalyzes the reaction listed as EC 4.1.1.23
-
-
-
additional information
?
-
-
enzyme from mammals is a bifunctional polypeptide, it also catalyzes the reaction listed as EC 4.1.1.23
-
-
-
additional information
?
-
-
enzyme from mammals is a bifunctional polypeptide, it also catalyzes the reaction listed as EC 4.1.1.23
-
-
-
additional information
?
-
-
relationship between OPRT, antagonizing dihydropyrimidine dehydrogenase, and clinicopathologic features in cancer and treatment with 5-fluorouracil, relation of patients survival and enzyme activities after surgery, detailed overview
-
-
-
additional information
?
-
-
the enzyme expression is weakly correlated to 5-fluorouracil sensitivity and apoptotic cell rate, overview
-
-
-
additional information
?
-
-
the enzyme is associated with thymidylate synthase and dihydropyrimidine dehydrogenase in resectable colorectal cancer, overview, prognostic impact of the enzyme among 5-fluorouracil metabolic enzymes in resectable colorectal cancers treated by oral 5-fluorouracil-based adjuvant chemotherapy, overview
-
-
-
additional information
?
-
-
half-of-sites binding of orotidine 5-phosphate and alpha-D-5-phosphorylribose 1-diphosphate to the enzyme supports an alternative variant of the Theorell-Chance mechanism with alternating site catalysis, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
-
-
-
?
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
essential enzyme for activation of 5-fluorouracil and its derivatives
-
-
?
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
the activating OPRT and its antagonist the catabolizing dihydropyrimidine dehydrogenase play important roles in 5-fluorouracil metabolism, overview
-
-
?
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
the enzyme is involved in degradation of 5-fluorouracil being the key enzyme related to the first-step activation process of 5-fluorouracil, and possibly predicts chemosensitivity to 5-fluorouracil, overview
-
-
?
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
the enzyme is involved in the de novo biosynthesis of pyrimidine nucleotides, main enzyme involved in phosphoribosylation of 5-fluorouracil, an essential step that leads to tumor growth inhibition
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
nucleotide-forming step in pyrimidine biosynthesis
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
final steps in biosynthesis of UMP
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
involved in de novo synthesis of pyrimidine nucleotides
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
-
involved in de novo synthesis of pyrimidine nucleotides
-
-
?
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
orotidine 5'-phosphate + diphosphate
show the reaction diagram
Plasmodium falciparum FCB
-
final steps in biosynthesis of UMP
-
-
?
orotidine 5-phosphate + diphosphate
orotate + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
?
5-fluorouracil + 5-phospho-alpha-D-ribose 1-diphosphate
5-fluorouridine 5'-phosphate + diphosphate
show the reaction diagram
-
the enzyme is involved in the metabolism of 5-fluorouracil, a chemotherapeutic drug in treatment of solid cancers, major pathways of 5-fluorouracil metabolism, overview
-
-
?
additional information
?
-
-
relationship between OPRT, antagonizing dihydropyrimidine dehydrogenase, and clinicopathologic features in cancer and treatment with 5-fluorouracil, relation of patients survival and enzyme activities after surgery, detailed overview
-
-
-
additional information
?
-
-
the enzyme expression is weakly correlated to 5-fluorouracil sensitivity and apoptotic cell rate, overview
-
-
-
additional information
?
-
-
the enzyme is associated with thymidylate synthase and dihydropyrimidine dehydrogenase in resectable colorectal cancer, overview, prognostic impact of the enzyme among 5-fluorouracil metabolic enzymes in resectable colorectal cancers treated by oral 5-fluorouracil-based adjuvant chemotherapy, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ba2+
-
slight activation
Ca2+
-
not activating
Ca2+
-
activation, 34% as effective as Mn2+ or Mg2+
Co2+
-
not activating
Co2+
-
slight activation
Mg2+
-
Km-value: 3 mM; requirement
Mg2+
-
best with 2 mM; mechanism; no orotate-Mg-complex formation, weak Mg-enzyme-complex; requirement
Mg2+
-
mechanism; requirement
Mg2+
-
requirement
Mg2+
-
requirement
Mg2+
-
requirement
Mg2+
-
required for substrate binding
Mg2+
-
required
Mg2+
P13298
Mg2+-dependent activity
Mg2+
-
Mg2+ is necessary for the activity of the enzyme and can be substituted for by Mn2+ and Co2+
Mn2+
-
activation; can replace Mg2+; mechanism
Mn2+
-
activation; mechanism
Mn2+
-
activation; can replace Mg2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1-deazaorotic acid
-
-
2,6-dihydroxypyridine-4-carboxylic acid
-
competitive to orotate, uncompetitive to 5-phospho-alpha-D-ribose 1-diphosphate
-
3-(2-hydroxybenzylidene)-2,6-dioxo-1,2,3,6-tetrahydropyridine-4-carboxylic acid
-
competitive to orotate, uncompetitive to 5-phospho-alpha-D-ribose 1-diphosphate
-
3-benzylidene-2,6-dioxo-1,2,3,6-tetrahydropyridine-4-carboxylic acid
-
competitive to orotate, uncompetitive to 5-phospho-alpha-D-ribose 1-diphosphate
-
5-aminoorotate
Q8N0R1
50% inhibition at 0.01 mM
5-azaorotic acid
-
-
5-bromoorotate
Q8N0R1
-
5-Bromouracil
-
-
5-Chlorouracil
-
-
5-Fluoroorotate
-
at 0.05 M
5-Fluoroorotate
Q8N0R1
50% inhibition at 2-10 nM
5-Fluorouracil
Q8N0R1
50% inhibition at 0.005-0.01 mM
5-iodoorotate
Q8N0R1
-
5-Methylorotate
Q8N0R1
50% inhibition at 0.001 mM
5-phospho-alpha-D-ribose 1-diphosphate
-
phosphorolysis, product inhibition, kinetics
5-phospho-alpha-D-ribose 1-diphosphate
-
phosphorolysis, product inhibition, kinetics
5-phospho-alpha-D-ribose 1-diphosphate
Q8N0R1
product inhibition, competitive to diphosphate, competitive to orotidine 5'-phosphate
6-hydroxy-5-((2-hydroxyethylamino)methyl)-2-oxo-1,2-dihydropyridine-4-carboxylic acid
-
competitive to orotate, uncompetitive to 5-phospho-alpha-D-ribose 1-diphosphate
-
adenine
-
not inhibitory
adenosine
-
-
adenosine
-
not inhibitory
ADP
-
not inhibitory
allopurinol
-
-
AMP
-
not inhibitory
arabinose 5-phosphate
-
at higher concentrations
ATP
-
not inhibitory
Azauracil
-
-
Azauridine
-
-
Barbituric acid
-
-
Co2+
-
inhibits Mg2+-activation
dihydroorotate
-
10 mM
diphosphate
-
-
diphosphate
-
product inhibition, kinetics
diphosphate
-
product inhibition, kinetics
diphosphate
Q8N0R1
product inhibition, noncompetitive to orotate, competitive to 5-phospho-alpha-D-ribose 1-diphosphate
diphosphate
L0T6H8, -
product inhibition
EDTA
-
5 mM, complete inhibition
erythrose 4-phosphate
-
at higher concentrations
fructose 1-phosphate
-
at higher concentrations
fructose 6-phosphate
-
at higher concentrations
HgCl2
-
slight inhibition of mutant, not wild-type
NEM
-
slight inhibition of mutant, not wild-type
Orotate
-
phosphorolysis, product inhibition, kinetics
Orotate
-
phosphorolysis, product inhibition, kinetics
Orotate
-
above 0.4 mM
Orotate
Q8N0R1
product inhibition, noncompetitive to diphosphate, competitive to orotidine 5'-phosphate
Orotic acid
-
when grown on glucose as carbon source, supplementation with orotic acid significantly decreases orotate phosphoribosyltransferase and orotidine 5'-monophoshate decarboxylase activities. In a strain deficient for dihydroorotase activity, orotic acid induces both phosphoribosyltransferase and orotidine 5'-monophoshate decarboxylase activites
Orotidine
-
10 mM
orotidine 5'-phosphate
Q8N0R1
product inhibition, competitive to 5-phospho-alpha-D-ribose 1-diphosphate, competitive to orotate
orotidine 5'-phosphate
L0T6H8, -
product inhibition
orotidylate
-
product inhibition, kinetics
orotidylate
-
product inhibition, kinetics
Oxipurinol
-
-
p-nitrophenyl beta-D-ribose
-
-
p-nitrophenyl beta-D-ribose 5'-phosphate
-
competitive inhibitor against orotidine 5'-phosphate
PCMB
-
reversible by DTT
PCMB
-
0.01 mM, complete inhibition
phosphate
-
-
phosphate
-
at higher concentrations
pyrazofurin
Q8N0R1
50% inhibition at 0.006-0.024 mM
ribose 5-phosphate
-
not inhibitory
ribose 5-phosphate
-
at higher concentrations
sulfate
-
competitive to diphosphate
UMP
-
1 mM, not 0.1 mM
UTP
-
not inhibitory
xanthosine-5'-phosphate
-
-
iodoacetamide
-
slight inhibition of mutant, not wild-type
additional information
-
not inhibitory: CMP, TMP, 6-aza-UMP or 5-bromo-UMP
-
additional information
-
no inhibition by SH-group reagents
-
additional information
-
structural features of pyrimidine nucleobase inhibitors
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
dithiothreitol
-
stimulating
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.025
-
5-Fluoroorotate
Q8N0R1
pH 8.0, 37C
0.0016
-
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.009
-
5-phospho-alpha-D-ribose 1-diphosphate
L0T6H8, -
ordered mechanism, pH 8.0, 25C
0.0113
-
5-phospho-alpha-D-ribose 1-diphosphate
Q8T6J6
37 C, pH 8.0, native enzyme complex
0.016
-
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.0164
-
5-phospho-alpha-D-ribose 1-diphosphate
Q8T6J6
37 C, pH 8.0, mixture of recombinant enzyme subunits
0.0282
-
5-phospho-alpha-D-ribose 1-diphosphate
Q8N0R1
pH 8.0, 37C
0.0286
-
5-phospho-alpha-D-ribose 1-diphosphate
Q8T6J6
37 C, pH 8.0, recombinant monofunctional enzyme
0.034
-
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.038
0.04
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.038
0.04
5-phospho-alpha-D-ribose 1-diphosphate
-
wild-type
0.041
-
5-phospho-alpha-D-ribose 1-diphosphate
P13298
wild type enzyme
0.043
-
5-phospho-alpha-D-ribose 1-diphosphate
P13298
mutant enzyme D131A
0.044
-
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.062
-
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.064
-
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.086
-
5-phospho-alpha-D-ribose 1-diphosphate
P13298
mutant enzyme D131A/D132A
0.096
-
5-phospho-alpha-D-ribose 1-diphosphate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
0.12
-
5-phospho-alpha-D-ribose 1-diphosphate
P13298
mutant enzyme D132A
0.36
-
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant
10.01
-
5-phospho-alpha-D-ribose 1-diphosphate
-
37 C, pH 8.0
0.013
-
diphosphate
-
wild-type
0.0143
-
diphosphate
Q8N0R1
pH 8.0, 37C
0.016
-
diphosphate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
0.036
-
diphosphate
-
-
0.096
-
diphosphate
-
phosphorolysis
0.22
0.25
diphosphate
-
-
0.002
-
Orotate
-
-
0.0045
-
Orotate
-
-
0.0045
-
Orotate
Q8T6J6
37 C, pH 8.0, mixture of recombinant enzyme subunits
0.0056
-
Orotate
-
37 C, pH 8.0
0.0056
-
Orotate
Q8T6J6
37 C, pH 8.0, native enzyme complex
0.0094
-
Orotate
L0T6H8, -
ordered mechanism, pH 8.0, 25C
0.01
-
Orotate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
0.0182
-
Orotate
Q8T6J6
37 C, pH 8.0, recombinant monofunctional enzyme
0.0182
-
Orotate
Q8N0R1
pH 8.0, 37C
0.025
-
Orotate
-
-
0.027
0.0275
Orotate
-
-
0.0276
-
Orotate
-
-
0.03
0.035
Orotate
-
wild-type
0.075
-
Orotate
-
-
0.44
-
Orotate
-
mutant
0.091
-
Orotidine
-
-
0.091
-
Orotidine
-
pH not specified in the publication, temperature not specified in the publication
0.091
-
Orotidine
-
pH 8.0, 25C
0.096
-
Orotidine
-
-
0.096
-
Orotidine
-
pH not specified in the publication, temperature not specified in the publication
0.096
-
Orotidine
-
pH 8.0, 25C
0.03
-
orotidine 5'-monophosphate
-
-
0.0015
-
orotidine 5'-phosphate
-
pH 8.0, 25C
0.00155
-
orotidine 5'-phosphate
-
in the presence of 1 mM diphosphate, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
0.0016
-
orotidine 5'-phosphate
-
pH not specified in the publication, temperature not specified in the publication
0.00214
-
orotidine 5'-phosphate
-
in the presence of 20 mM phosphonoacetic acid, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
0.0026
-
orotidine 5'-phosphate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
0.0029
-
orotidine 5'-phosphate
-
in the presence of 20 mM phosphonoacetic acid, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
0.0031
0.0036
orotidine 5'-phosphate
-
wild-type
0.0037
-
orotidine 5'-phosphate
-
pH not specified in the publication, temperature not specified in the publication
0.0037
-
orotidine 5'-phosphate
-
pH 8.0, 25C
0.00373
-
orotidine 5'-phosphate
-
in the presence of 1 mM diphosphate, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
0.004
-
orotidine 5'-phosphate
P13298
wild type enzyme
0.007
-
orotidine 5'-phosphate
P13298
mutant enzyme D131A; mutant enzyme D132A
0.008
0.0083
orotidine 5'-phosphate
-
-
0.008
0.0083
orotidine 5'-phosphate
-
phosphorolysis
0.01
-
orotidine 5'-phosphate
P13298
mutant enzyme D131A/D132A
0.0251
-
orotidine 5'-phosphate
Q8N0R1
pH 8.0, 37C
0.045
-
orotidine 5'-phosphate
-
-
1.59
-
Phosphonoacetic acid
-
-
3.84
-
Phosphonoacetic acid
-
-
0.22
0.25
diphosphate
-
-
additional information
-
additional information
-
principles of assay
-
additional information
-
additional information
-
principles of assay
-
additional information
-
additional information
-
kinetic study
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
HPLC microassay
-
additional information
-
additional information
-
detailed kinetic analysis, isothermal titration calorimetry, the double Theorell-Chance mechanism yields a steady-state rate equation indistinguishable in form from the observed classical ping-pong bi-bi kinetics, steady-state kinetics, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
4
-
5-Fluoroorotate
Q8N0R1
pH 8.0, 37C
3.2
-
5-phospho-alpha-D-ribose 1-diphosphate
Q8N0R1
pH 8.0, 37C
0.28
-
diphosphate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
1.3
-
diphosphate
Q8N0R1
pH 8.0, 37C
0.6
-
Orotate
L0T6H8, -
ordered mechanism, pH 8.0, 25C
0.61
-
Orotate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
3
-
Orotate
Q8N0R1
pH 8.0, 37C
4.2
-
Orotate
Q8T6J6
37 C, pH 8.0, recombinant monofunctional enzyme
5.4
-
Orotate
-
37 C, pH 8.0
6
-
Orotate
Q8T6J6
37 C, pH 8.0, mixture of recombinant enzyme subunits
10.8
-
Orotate
Q8T6J6
37 C, pH 8.0, native enzyme complex
0.024
-
Orotidine
-
-
0.024
-
Orotidine
-
pH 8.0, 25C
0.042
-
Orotidine
-
-
0.042
-
Orotidine
-
pH 8.0, 25C
0.014
-
orotidine 5'-phosphate
-
in the presence of 20 mM phosphonoacetic acid, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
0.017
-
orotidine 5'-phosphate
-
in the presence of 20 mM phosphonoacetic acid, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
0.1
-
orotidine 5'-phosphate
-
in the presence of 1 mM diphosphate, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
0.28
-
orotidine 5'-phosphate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
1.96
-
orotidine 5'-phosphate
-
in the presence of 1 mM diphosphate, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
2.6
-
orotidine 5'-phosphate
Q8N0R1
pH 8.0, 37C
0.017
-
Phosphonoacetic acid
-
-
0.023
-
Phosphonoacetic acid
-
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
6
-
5-phospho-alpha-D-ribose 1-diphosphate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
5436
6.6
-
5-phospho-alpha-D-ribose 1-diphosphate
L0T6H8, -
ordered mechanism, pH 8.0, 25C
5436
10
-
diphosphate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
22042
60
-
Orotate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
14840
64
-
Orotate
L0T6H8, -
ordered mechanism, pH 8.0, 25C
14840
0.26
-
Orotidine
-
pH 8.0, 25C
14843
0.44
-
Orotidine
-
pH 8.0, 25C
14843
4.8
-
orotidine 5'-phosphate
-
in the presence of 20 mM phosphonoacetic acid, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
14844
7.9
-
orotidine 5'-phosphate
-
in the presence of 20 mM phosphonoacetic acid, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
14844
65
-
orotidine 5'-phosphate
-
in the presence of 1 mM diphosphate, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
14844
100
-
orotidine 5'-phosphate
L0T6H8, -
ping-pong mechanism, pH 8.0, 25C
14844
530
-
orotidine 5'-phosphate
-
in the presence of 1 mM diphosphate, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
14844
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00047
-
1-deazaorotic acid
-
-
0.00025
-
2,6-dihydroxypyridine-4-carboxylic acid
-
competitive to orotate, pH 8.0, 25C
-
0.0082
-
2,6-dihydroxypyridine-4-carboxylic acid
-
uncompetitive to 5-phospho-alpha-D-ribose 1-diphosphate, pH 8.0, 25C
-
0.0074
-
3-(2-hydroxybenzylidene)-2,6-dioxo-1,2,3,6-tetrahydropyridine-4-carboxylic acid
-
competitive to orotate, pH 8.0, 25C
-
0.014
-
3-(2-hydroxybenzylidene)-2,6-dioxo-1,2,3,6-tetrahydropyridine-4-carboxylic acid
-
uncompetitive to 5-phospho-alpha-D-ribose 1-diphosphate, pH 8.0, 25C
-
0.00019
-
3-benzylidene-2,6-dioxo-1,2,3,6-tetrahydropyridine-4-carboxylic acid
-
competitive to orotate, pH 8.0, 25C
-
0.0065
-
3-benzylidene-2,6-dioxo-1,2,3,6-tetrahydropyridine-4-carboxylic acid
-
uncompetitive to 5-phospho-alpha-D-ribose 1-diphosphate, pH 8.0, 25C
-
0.0021
-
5-azaorotic acid
-
-
0.0482
-
5-bromoorotate
Q8N0R1
pH 8.0, 37C
0.0954
-
5-Fluoroorotate
Q8N0R1
pH 8.0, 37C
0.0561
-
5-Fluorouracil
Q8N0R1
pH 8.0, 37C
0.0153
-
5-iodoorotate
Q8N0R1
pH 8.0, 37C
0.0214
-
5-Methylorotate
Q8N0R1
pH 8.0, 37C
0.042
-
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.0423
-
5-phospho-alpha-D-ribose 1-diphosphate
Q8N0R1
pH 8.0, 37C, cosubstrate diphosphate
0.1501
-
5-phospho-alpha-D-ribose 1-diphosphate
Q8N0R1
pH 8.0, 37C, cosubstrate orotidine 5'-phosphate
0.0062
-
6-hydroxy-5-((2-hydroxyethylamino)methyl)-2-oxo-1,2-dihydropyridine-4-carboxylic acid
-
competitive to orotate, pH 8.0, 25C
-
0.0135
-
6-hydroxy-5-((2-hydroxyethylamino)methyl)-2-oxo-1,2-dihydropyridine-4-carboxylic acid
-
uncompetitive to 5-phospho-alpha-D-ribose 1-diphosphate, pH 8.0, 25C
-
0.026
-
diphosphate
L0T6H8, -
mixed type inhibition, 5-phospho-alpha-D-ribose 1-diphosphate varied substrate, orotate unsaturated, pH 8.0, 25C
0.029
-
diphosphate
L0T6H8, -
mixed type inhibition, orotate varied substrate, 5-phospho-alpha-D-ribose 1-diphosphate unsaturated, pH 8.0, 25C
0.0797
-
diphosphate
Q8N0R1
pH 8.0, 37C, cosubstrate orotate
0.108
-
diphosphate
L0T6H8, -
noncompetitive, 5-phospho-alpha-D-ribose 1-diphosphate varied substrate, orotate saturated, pH 8.0, 25C
0.125
-
diphosphate
Q8N0R1
pH 8.0, 37C, cosubstrate 5-phospho-alpha-D-ribose 1-diphosphate
0.131
-
diphosphate
-
-
0.209
-
diphosphate
L0T6H8, -
mixed type inhibition, orotate varied substrate, 5-phospho-alpha-D-ribose 1-diphosphate saturated, pH 8.0, 25C
0.0075
-
Orotate
Q8N0R1
pH 8.0, 37C, cosubstrate orotidine 5'-phosphate
0.0213
-
Orotate
Q8N0R1
pH 8.0, 37C, cosubstrate diphosphate
0.00044
-
orotidine 5'-phosphate
L0T6H8, -
mixed type inhibition, 5-phospho-alpha-D-ribose 1-diphosphate varied substrate, orotate unsaturated, pH 8.0, 25C
0.001
-
orotidine 5'-phosphate
L0T6H8, -
mixed type inhibition, 5-phospho-alpha-D-ribose 1-diphosphate varied substrate, orotate saturated, pH 8.0, 25C
0.0074
-
orotidine 5'-phosphate
L0T6H8, -
mixed type inhibition, orotate varied substrate, 5-phospho-alpha-D-ribose 1-diphosphate unsaturated, pH 8.0, 25C
0.0157
-
orotidine 5'-phosphate
Q8N0R1
pH 8.0, 37C, cosubstrate 5-phospho-alpha-D-ribose 1-diphosphate
0.0241
-
orotidine 5'-phosphate
Q8N0R1
pH 8.0, 37C, cosubstrate orotate
0.035
-
orotidine 5'-phosphate
L0T6H8, -
noncompetitive, orotate varied substrate, 5-phospho-alpha-D-ribose 1-diphosphate saturated, pH 8.0, 25C
0.0063
-
orotydilate
-
plus 5-phospho-alpha-D-ribose 1-diphosphate
-
0.0083
-
orotydilate
-
plus orotate
-
0.01
-
orotydilate
-
-
-
0.000121
-
p-nitrophenyl beta-D-ribose
-
in the presence of orotidine 5'-phosphate, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
0.000188
-
p-nitrophenyl beta-D-ribose
-
in the presence of orotidine 5'-phosphate, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
4e-05
-
p-nitrophenyl beta-D-ribose 5'-phosphate
-
in the presence of orotidine 5'-phosphate, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
4.1e-05
-
p-nitrophenyl beta-D-ribose 5'-phosphate
-
in the presence of orotidine 5'-phosphate, at 25C, 50 mM Tris-HCl, pH 8.0, 5 mM MgCl2
0.0705
-
pyrazofurin
Q8N0R1
pH 8.0, 37C
2.7
-
sulfate
-
orotidine 5'-phosphate as substrate, pH not specified in the publication, temperature not specified in the publication
3.1
-
sulfate
-
orotidine 5'-phosphate as substrate, pH not specified in the publication, temperature not specified in the publication
10.8
-
sulfate
-
orotidine 5'-phosphate as substrate, pH not specified in the publication, temperature not specified in the publication
17.6
-
sulfate
-
orotidine 5'-phosphate as substrate, pH not specified in the publication, temperature not specified in the publication
0.1212
-
Uracil
Q8N0R1
pH 8.0, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.5e-06
-
-
untransfected TMK-1 cells
9e-06
-
-
untransfected MKN-45 cells
7.2e-05
-
-
transfected MKN-45-OPRT cells
0.000172
-
-
transfected TMK-OPRT cells
0.115
-
-
-
0.41
-
-
mutant
0.69
-
-
-
3
8
P13298
wild type enzyme
4.32
-
-
37 C, pH 8.0
15.2
-
-
wild-type
24
-
-
recombinant enzyme from crude cell extract, in the presence of Mg2+
45
-
-
in the absence of added OMP-decarboxylase, EC 4.1.1.23
65
-
-
in the presence of added OMP-decarboxylase, EC 4.1.1.23
71
-
-
recombinant enzyme after 17fold purification, in the presence of Co2+
105
-
L0T6H8, -
pH 8.0, 25C
225
-
-
recombinant enzyme after 17fold purification, in the presence of Mn2+
423
-
-
recombinant enzyme after 17fold purification, in the presence of Mg2+
additional information
-
-
-
additional information
-
-
-
additional information
-
-
ELISA assay method development and evaluation for enzyme detection and quantification in cancer tissue, overview
additional information
-
-
enzyme expression rate in tumor tissue with or without treatment with 5-fluorouracil
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
6.5
-
reverse (pyrophosphorolysis) reaction
7
7.5
-
preferred buffer: Tris-HCl, when substrates are non-saturating, phosphate buffer, when substrate are saturating, not: maleate, imidazole, N-tris[hydroxymethyl] methyl-2-aminoethane-sulfonic acid (i.e. TES) or 3-[N-morpholino]-2-hydroxypropanesulfonic acid (i.e. MOPS) buffer
7.4
-
-
assay at
7.5
-
-
assay at
7.6
-
-
assay at
7.8
-
-
assay at
8
-
-
assay at
8.5
-
-
mutant
9.5
-
-
wild-type
10
-
-
recombinant enzyme
10.5
11.5
-
forward (phosphoribosyl transfer) reaction
additional information
-
-
2 isozymes: pI: 5.65 (minor form), pI: 5.85 (major form)
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
8
Q8T6J6
recombinant monofunctional enzyme
7.2
9.2
-
about half-maximal activity at pH 7.2 and about 70% of maximal activity at pH 9.2
7.2
9.5
-
about half-maximal activity at pH 7.2 and 9.5, mutant
8.5
10.5
-
about half-maximal activity at pH 8.5 and about 70% of maximal activity at pH 10.5, wild-type
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20
-
-
assay at
30
-
-
assay at
37
-
-
assay at
37
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.4
-
-
predicted from amino acid sequence
7.1
-
Q8N0R1
calculated
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
in resectable colorectal cancer
Manually annotated by BRENDA team
-
colorectal cancer tissue
Manually annotated by BRENDA team
-
colorectal cancer, 150 patients with cancer at different stages, stage-related enzyme expression level, overview
Manually annotated by BRENDA team
-
Dukes B and C colorectal carcinoma cells
Manually annotated by BRENDA team
-
in normal non-neoplastic colorectal epithelium, granular staining is observed only in the crypt
Manually annotated by BRENDA team
-
in gallbladder carcinoma, mucosal neoplastic epithelium shows dense cytoplasmic expression but expression is absent in the deeply invasive lesions
Manually annotated by BRENDA team
-
mucosal neoplastic epithelium, granular expression
Manually annotated by BRENDA team
-
221 specimen, expression profile of the enzyme and its antagonist dihydropyrimidine dehydrogenase both active in 5-fluorouracil metabolism, the enzyme expression levels correlate, overview
Manually annotated by BRENDA team
-
OPRT levels are high in well differentiated and localized gastric carcinomas and are significantly higher in gastric carcinoma tissue than in normal gastric mucosa
Manually annotated by BRENDA team
-
OPRT is involved in early events of invasion of hepatocellular carcinoma cells
Manually annotated by BRENDA team
-
gastric cancer cell line with low baseline expression levels of OPRT
Manually annotated by BRENDA team
-
OPRT is involved in early events of pancreatic carcinogenesis
Manually annotated by BRENDA team
-
normal tissue, hormone-sensitive prostate cancer (HSPC) or hormonerefractory prostate cancer (HRPC) tissue
Manually annotated by BRENDA team
-
gastric cancer cell line with low baseline expression levels of OPRT
Manually annotated by BRENDA team
-
parent gastric cancer cell line
Manually annotated by BRENDA team
additional information
-
the enzyme expression is increased in tumor tissue compared to non-tumor tissue
Manually annotated by BRENDA team
additional information
-
expression analysis in carcinoma cell lines, no expression in pancreatic ducts and PanIN-1A cells, overview
Manually annotated by BRENDA team
additional information
-
NCI-60 cell panel
Manually annotated by BRENDA team
additional information
-
in mucosal carcinoma lesions frequency of OPRT expression is 32.1%, in infiltrative lesions frequency of OPRT expression is 69.8%. In lymphovascularly invasive lesions frequency of OPRT expression is 88.2% and in metastatic lymph nodes frequency of OPRT expression is 88.8%
Manually annotated by BRENDA team
additional information
-
MKN-45/F2R cell, 5-fluorouracil resistant gastric cancer cell line
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
in metastatic lymph nodes and lymphovascularly invasive lesions
Manually annotated by BRENDA team
Plasmodium falciparum FCB
-
-
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Aeropyrum pernix (strain ATCC 700893 / DSM 11879 / JCM 9820 / NBRC 100138 / K1)
Burkholderia cenocepacia (strain ATCC BAA-245 / DSM 16553 / LMG 16656 / NCTC 13227 / J2315 / CF5610)
Escherichia coli (strain K12)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Leishmania donovani (strain BPK282A1)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Streptococcus mutans serotype c (strain ATCC 700610 / UA159)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
38000
-
L0T6H8, -
gel filtration
39000
-
-
gel filtration
40000
-
-
gel filtration
45400
-
-
native enzyme, gel filtration
47000
-
-
K-12, gel filtration
50000
-
-
sucrose density gradient centrifugation
52000
-
-
Western blot analyis
67000
-
Q8T6J6
gel filtration, recombinant enzyme
67000
-
Q8N0R1
gel filtration, recombinant enzyme
140000
-
-
gel filtration
140000
-
Q8T6J6
gel filtration and SDS-PAGE of native enzyme crosslinked with dimethyl suberimidate
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 51500, SDS-PAGE, sedimentation studies reveal monomer or dimer, enzyme activity and orotidine 5'-monophosphate decarboxylating activity on a single polypeptide
?
-
x * 2000, SDS-PAGE
?
-
x * 24700, SDS-PAGE, recombinant enzyme
?
-
x * 52000, SDS-PAGE
dimer
-
2 * 20000, SDS-PAGE
dimer
-
2 * 23500, SDS-PAGE
dimer
-
2 * 22000, SDS-PAGE
dimer
-
homodimer, crystalline structure
dimer
-
homodimer, with catalytically important residues from one subunit available for the other, crystalline structure
dimer
Q8T6J6
2 * 32000, SDS-PAGE, recombinant enzyme
dimer
Q8N0R1
2 * 33400, recombinant enzyme, SDS-PAGE, 2 * 33000, calculated
dimer
-
homodimer
homodimer
P13298
x-ray crystallography
homodimer
-
2 * 21300, SDS-PAGE
homodimer
Q8DTV2, -
2 * 27000, SDS-PAGE, gel filtration
homodimer
L0T6H8, -
2 * 20000, SDS-PAGE, gel filtration; 2 * 18761, mass spectrometry, gel filtration
tetramer
-
2 * 32000, enzyme subunit, + 2 * 38000, orotidine 5-monophosphate decarboxylase subunit, SDS-PAGE
tetramer
Q8T6J6
2 * 32000, enzyme subunit, + 2 * 38000, orotidine 5-monophosphate decarboxylase subunit, SDS-PAGE, native enzyme
monomer
-
1 * 51500, SDS-PAGE, enzyme activity and orotidine 5'-monophosphate decarboxylating activity on a single polypeptide
additional information
-
active site of enzyme requires D125 of one subunit and K103 of second subunit
additional information
-
N-terminal amino acid analysis
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ligated with sulfate, homodimer
-
sitting-drop vapour-diffusion method, polyethylene glycol 300
-
sitting drop vapour diffusion method, the apoenzyme is crystallized in 100 mM Tris-HCl, pH 7.4, 0.2 M magnesium acetate, and 26% (w/v) PEG 6000, crystals of OPRTase in complex with substrates (5.0 mM 5-phospho-alpha-D-ribose 1-diphosphate and 5.0 mM orotate) or product (5.0 mM orotidine 5'-phosphate) are grown in 100 mM sodium acetate, pH 4.6, 0.14 M ammonium acetate, and 38% (w/v) PEG 4000, crystals of the OMP complex are grown from solutions containing 100 mM Tris HCl, pH 7.4, 0.08 M magnesium acetate, and 28% (w/v) PEG 6000
P13298
complexed with orotidine monophosphate, homodimer, with catalytically important residues from one subunit available for the other
-
hanging-grop vapour-diffusion method, 2.3 M ammonium sulfate, pH 8.6
Q8DTV2, -
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
9
-
stable
7.5
9.5
-
at least 6 months stable, -20C
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
50
-
-
OPRTase activity decreases with the increase in incubation temperature and more than 50% of the activity is lost upon incubation at 50C for 30 min
90
-
-
20 min, 70% of activity remaining
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
0.05 mM UMP and 1% polyethyleneglycol stabilize during final stage of purification
-
5 mM Mg2+, 1 mM phosphoribose diphosphate and 2 mM DTT stabilize dilute enzyme solutions
-
dialysis against phosphate buffer, pH 7 or 7.5, unstable to, 2 mM DTT protect
-
dilution inactivates
-
phosphate, 0.3 M and above, stabilizes
-
proteins, e.g. albumin, do not stabilize dilute enzyme solutions
-
native enzyme complex, stable for at least 6 months at -20C or -80C in 50 mM Hepes, pH 7.4, 300 mM NaCl, 5 mM dithiothreitol, 20% glycerol. At 4C, loss of 50% of activity within 4 weeks.
Q8T6J6
recombinant enzyme dimer, stable for at least 3 months at -20C or -80C in 50 mM Hepes, pH 7.4, 5 mM dithiothreitol, 20% glycerol. In absence of dithiothreitol and glycerol, loss of 50% of activity during overnight storage at 4C.
Q8T6J6
recombinant enzyme, stable for at least 3 months at 4C or -20C in presence of 1 mM dithiothreitol and 10% glycerol
Q8N0R1
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, 50 mM Tris-HCl, 2 mM EDTA, 2 mM mercaptoethanol, pH 6.4, several months, no apparent loss of activity
-
-25C, in 50% v/v glycerol, 0.1 mM DTT, about 35% loss of activity within 40 days
-
-20C, concentrated enzyme solution, at least 4 months
-
-60C to-20C, crude enzyme or ammonium sulfate preparation, 2 years
-
frozen, partially purified enzyme in phosphate buffer, pH 7 or 7.5, 2 months
-
-80C, stable up to 12 months, 5% glycerol, pH 8.0
L0T6H8, -
4C, t1/2: 1.5 days
-
-20C, pH 7.5-9.5, at least 6 months
-
-76C, at least 6 months
-
4C, gradual loss of activity at pH 7.5-9.5
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ammonium sulfate precipitation, DEAE-Sepharose Fast Flow column chromatography, and Superdex-75 gel filtration
-
OMP-agarose affinity chromatography
-
Ni2+ affinity column
-
partial, rapid tandem affinity column method
-
anion exchange chromatography, gel filtration, hydrophobic interaction chromatography
L0T6H8, -
from in vitro cultivation of organism
-
immobilized metal ion affinity chromatography (Ni2+)
-
Ni2+ affinity column
-
recombinant enzyme
Q8N0R1
recombinant enzyme
-
immobilized metal ion affinity chromatography (Co2+), His-tag cleavage (TEV protease), immobilized metal ion affinity chromatography (Co2+)
-
partial, affinity chromatography on Blue-Dextran- or Cibacron Blue F3GA-Sepharose
-
immobilized metal ion affinity chromatography (Ni2+), gel filtration
Q8DTV2, -
recombinant enzyme
-
partial, not separable from EC 4.1.1.23
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli DH5alpha cells
-
expressed from pDEST14-OPRT in Escherichia coli BL21-AI competent cells
-
expressed in Escherichia coli
-
OPRT, stable overexpression in the gastric cancer cell lines TMK-1 and MKN-45, enhancing the effect of 5-fluorouracil on the cells, transfected cells show a similar growth curve as the wild-type parent cells, while the drug sensitivity is increased compared to the untransfected cells, overview
-
expressed in Escherichia coli BL21(DE3)
L0T6H8, -
expressed in Escherichia coli
-
His-tagged protein expressed in Escherichia coli BL21(DE3), gel filtration
-
into the pDONR221 vector, expressed from pDEST14-OPRT in Escherichia coli BL21-AI competent cells
-
structural gene pyrE
-
His-tagged protein expressed in Escherichia coli BL21(DE3)
-
mutants are expressed in Escherichia coli strain CS101-4UI
P13298
structural gene pyrE, subcloned from a genomic library in pBR328(pAV002), transduced into pyr-auxotroph Salmonella typhimurium strain SA2434 with phage P22, finally cloned to and expressed in overproducing strain Escherichia coli MB13
-
His-tagged protein expressed in Escherichia coli BL21(DE3)
Q8DTV2, -
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
non-cancerous components do not express OPRT
-
mRNA expression of OPRT is markedly decreased to 12.4% and activity to 46.9% in the 5-fluorouracil resistant MKN-45/F2R cell line compared to the MKN-45 parent cell line. OPRT gene expression is markedly decreased to 14.4% when down-regulated by siRNA
-
low expression in normal prostate gland tissue
-
lexpression of OPRT in mucosal carcinoma components, in infiltrative components, in lymphovascularly invasive lesions and in metastatic lymph nodes. No significant correlation between OPRT expression and cancer stage, T-grade or N-grade, but OPRT expression correlates positively with the presence of lymphovascular invasion. OPRT is diffusely expressed to a greater extent, especially in the tumor cells adjacent to the infiltrative margin
-
strong expression of OPRT in prostate cancer cells, significant correlation between OPRT mRNA expression levels and the tumor pathological grade. The OPRT/dihydropyrimidine dehydrogenase expression ratio in the HRPC group is significantly higher than that in the low grade HSPC group
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
G133D
-
no enzymic activity
G133D
Mortierella alpina 1S-4
-
no enzymic activity
-
D131A
P13298
severly reduced activity
D131A/D132A
P13298
severly reduced activity
D132A
P13298
severly reduced activity
D125N
-
active site of enzyme requires D125 of one subunit and K103 of second subunit
G213A
-
OPRT, the gene polymorphism predicts toxicity in patients treated with bolus 5-fluorouracil regimen, the Ala allele in the enzyme G213A polymorphism and the two tandem repeats in the TYMS promoter polymorphism are associated with grade 3 to 4 neutropenia and diarrhea, distribution in 69 patients samples, genotyping, relationship between OPRT mRNA expression and the OPRT G213A polymorphism, overview
additional information
-
mutational separation of catalytic activity of enzyme and EC4.1.1.23 activity results in active but unstable proteins
K103A
-
active site of enzyme requires D125 of one subunit and K103 of second subunit
additional information
-
point mutations for negative complementation of enzyme activity
additional information
-
deletion of 1-5 C-terminal amino acids, activities reduced to 22%-75% of wild type activity
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
diagnostics
-
OPRT activity in tumor tissue is a predictor of prognosis in resectable CRC patients treated by oral 5-fluorouracil-based adjuvant chemotherapy, and is useful to pick-up high risk patients independent from known prognosis factors
diagnostics
-
OPRT and DPD are valuable prognostic markers in gastric cancer
medicine
-
enzyme activity is 7.5fold enhanced in bladder carcinoma compared to normal. Bladder carcinoma subtypes show distinct levels of enzyme activity and there is positive association between the activity levels of enzyme and thymidylate synthase/thymidine kinase. Enzyme activity in bladder carcinoma cells also correlates positively with their sensitivity to 5-fluorouracil
medicine
-
immunochemical detection of tumoral enzyme expression by antibody, method for predicting the clinical response to 5-fluorouracil-based chemotherapy
medicine
-
OPRT expression is negatively associated with colorectal cancer progression
medicine
-
the OPRT mRNA level is positively correlated with the 5-fluorouracil efficacy in antitumor therapy
medicine
-
OPRT activity is significantly lower in tumors with lymph node metastasis than in tumors lacking lymph node metastasis, thus OPRT activity level in tumor tissue may be an important prognostic factor for survival in Dukes B and C colorectal carcinoma cells with radical resection and adjuvant chemotherapy with orally administered tegafur/uracil
medicine
-
the expression of OPRT may be useful to predict the response to adjuvant chemotherapy with 5-fluorouracil in human pancreatic cancer