BRENDA - Enzyme Database

Thiolactomycin inhibits D-aspartate oxidase: a novel approach to probing the active site environment

Katane, M.; Saitoh, Y.; Hanai, T.; Sekine, M.; Furuchi, T.; Koyama, N.; Nakagome, I.; Tomoda, H.; Hirono, S.; Homma, H.; Biochimie 92, 1371-1378 (2010)

Data extracted from this reference:

Cloned(Commentary)
EC Number
Commentary
Organism
1.4.3.1
expression of GST-tagged, N-terminally His-tagged, and S-tagged DDO
Mus musculus
Engineering
EC Number
Amino acid exchange
Commentary
Organism
1.4.3.1
R237A
site-directed mutagenesis, active site mutant, shows reduced binding of inhibitor thiolactomycin compared to the wild-type enzyme
Mus musculus
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
1.4.3.1
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methyl-1,3-butadienyl]-2(5H)-thiophenone
i.e. thiolactomycin, active site-directed DDO inhibitor, competitive inhibition, competes with both the substrate and the coenzyme FAD; i.e. thiolactomycin, competitive inhibition, competes with both the substrate and the coenzyme FAD
Homo sapiens
1.4.3.1
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methyl-1,3-butadienyl]-2(5H)-thiophenone
i.e. thiolactomycin, active site-directed DDO inhibitor involving binding via Arg237, mixed type of inhibition, competes with both the substrate and the coenzyme FAD, structural models of mouse DDO/TLM complexes; i.e. thiolactomycin, competitive inhibition, competes with both the substrate and the coenzyme FAD
Mus musculus
1.4.3.1
malonate
competitive inhibition
Mus musculus
1.4.3.1
malonate
-
Homo sapiens
1.4.3.1
meso-tartrate
competitive inhibition
Mus musculus
1.4.3.1
meso-tartrate
-
Homo sapiens
1.4.3.3
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methyl-1,3-butadienyl]-2(5H)-thiophenone
i.e. thiolactomycin, competitive inhibition, competes with both the substrate and the coenzyme FAD
Sus scrofa
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.4.3.1
D-aspartate + H2O + O2
Mus musculus
-
oxaloacetate + NH3 + H2O2
-
-
?
1.4.3.1
D-aspartate + H2O + O2
Homo sapiens
-
oxaloacetate + NH3 + H2O2
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
1.4.3.1
Homo sapiens
-
-
-
1.4.3.1
Mus musculus
-
; male ICR mice
-
1.4.3.3
Sus scrofa
-
-
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
1.4.3.1
Hep-G2 cell
-
Homo sapiens
-
1.4.3.3
commercial preparation
-
Sus scrofa
-
1.4.3.3
kidney
-
Sus scrofa
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.4.3.1
D-aspartate + H2O + O2
-
711325
Mus musculus
oxaloacetate + NH3 + H2O2
-
-
-
?
1.4.3.1
D-aspartate + H2O + O2
-
711325
Homo sapiens
oxaloacetate + NH3 + H2O2
-
-
-
?
1.4.3.1
additional information
structure-function relationships of DDO, overview
711325
Mus musculus
?
-
-
-
-
1.4.3.1
additional information
structure-function relationships of DDO, overview
711325
Homo sapiens
?
-
-
-
-
Temperature Optimum [°C]
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
1.4.3.1
37
-
assay at
Mus musculus
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.4.3.1
8.3
-
assay at
Mus musculus
Cofactor
EC Number
Cofactor
Commentary
Organism
Structure
1.4.3.1
FAD
-
Homo sapiens
1.4.3.1
FAD
-
Mus musculus
1.4.3.3
FAD
-
Sus scrofa
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
1.4.3.1
additional information
-
additional information
inhibition kinetics
Mus musculus
1.4.3.1
0.66
-
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methyl-1,3-butadienyl]-2(5H)-thiophenone
pH 8.3, 37°C
Mus musculus
1.4.3.1
1.59
-
malonate
pH 8.3, 37°C
Mus musculus
1.4.3.1
1.94
-
meso-tartrate
pH 8.3, 37°C
Mus musculus
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
1.4.3.1
1.86
-
pH 8.3, 37°C
Mus musculus
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methyl-1,3-butadienyl]-2(5H)-thiophenone
1.4.3.1
5.3
-
pH 8.3, 37°C
Mus musculus
malonate
1.4.3.1
8.71
-
pH 8.3, 37°C
Mus musculus
meso-tartrate
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
1.4.3.1
expression of GST-tagged, N-terminally His-tagged, and S-tagged DDO
Mus musculus
Cofactor (protein specific)
EC Number
Cofactor
Commentary
Organism
Structure
1.4.3.1
FAD
-
Homo sapiens
1.4.3.1
FAD
-
Mus musculus
1.4.3.3
FAD
-
Sus scrofa
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
1.4.3.1
R237A
site-directed mutagenesis, active site mutant, shows reduced binding of inhibitor thiolactomycin compared to the wild-type enzyme
Mus musculus
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
1.4.3.1
1.86
-
pH 8.3, 37°C
Mus musculus
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methyl-1,3-butadienyl]-2(5H)-thiophenone
1.4.3.1
5.3
-
pH 8.3, 37°C
Mus musculus
malonate
1.4.3.1
8.71
-
pH 8.3, 37°C
Mus musculus
meso-tartrate
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
1.4.3.1
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methyl-1,3-butadienyl]-2(5H)-thiophenone
i.e. thiolactomycin, active site-directed DDO inhibitor, competitive inhibition, competes with both the substrate and the coenzyme FAD; i.e. thiolactomycin, competitive inhibition, competes with both the substrate and the coenzyme FAD
Homo sapiens
1.4.3.1
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methyl-1,3-butadienyl]-2(5H)-thiophenone
i.e. thiolactomycin, active site-directed DDO inhibitor involving binding via Arg237, mixed type of inhibition, competes with both the substrate and the coenzyme FAD, structural models of mouse DDO/TLM complexes; i.e. thiolactomycin, competitive inhibition, competes with both the substrate and the coenzyme FAD
Mus musculus
1.4.3.1
malonate
competitive inhibition
Mus musculus
1.4.3.1
malonate
-
Homo sapiens
1.4.3.1
meso-tartrate
competitive inhibition
Mus musculus
1.4.3.1
meso-tartrate
-
Homo sapiens
1.4.3.3
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methyl-1,3-butadienyl]-2(5H)-thiophenone
i.e. thiolactomycin, competitive inhibition, competes with both the substrate and the coenzyme FAD
Sus scrofa
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
1.4.3.1
additional information
-
additional information
inhibition kinetics
Mus musculus
1.4.3.1
0.66
-
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methyl-1,3-butadienyl]-2(5H)-thiophenone
pH 8.3, 37°C
Mus musculus
1.4.3.1
1.59
-
malonate
pH 8.3, 37°C
Mus musculus
1.4.3.1
1.94
-
meso-tartrate
pH 8.3, 37°C
Mus musculus
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.4.3.1
D-aspartate + H2O + O2
Mus musculus
-
oxaloacetate + NH3 + H2O2
-
-
?
1.4.3.1
D-aspartate + H2O + O2
Homo sapiens
-
oxaloacetate + NH3 + H2O2
-
-
?
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
1.4.3.1
Hep-G2 cell
-
Homo sapiens
-
1.4.3.3
commercial preparation
-
Sus scrofa
-
1.4.3.3
kidney
-
Sus scrofa
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.4.3.1
D-aspartate + H2O + O2
-
711325
Mus musculus
oxaloacetate + NH3 + H2O2
-
-
-
?
1.4.3.1
D-aspartate + H2O + O2
-
711325
Homo sapiens
oxaloacetate + NH3 + H2O2
-
-
-
?
1.4.3.1
additional information
structure-function relationships of DDO, overview
711325
Mus musculus
?
-
-
-
-
1.4.3.1
additional information
structure-function relationships of DDO, overview
711325
Homo sapiens
?
-
-
-
-
Temperature Optimum [°C] (protein specific)
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
1.4.3.1
37
-
assay at
Mus musculus
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.4.3.1
8.3
-
assay at
Mus musculus