Cloned (Comment) | Organism |
---|---|
expression of c-myc-tagged enzyme mutants in Pichia pastoris membranes | Rattus norvegicus |
gene rVkorc1, expression of C-terminally c-myc-tagged wild-type and mutant enzymes in Pichia patoris strain SMD1168 as membrane-bound proteins | Rattus norvegicus |
Protein Variants | Comment | Organism |
---|---|---|
L120Q | naturally occuring mutant, resitant to warfarin and other anticoagulants | Rattus norvegicus |
L120Q | naturally occuring mutant, the mutant rat is resistant to some anticoagulants | Rattus norvegicus |
L120Q/L128Q/Y139C/Y139F/Y139S | site-directed mutagenesis | Rattus norvegicus |
L128Q | naturally occuring mutant, resitant to warfarin and other anticoagulants | Rattus norvegicus |
L128Q | naturally occuring mutant, the mutant rat is resistant to some anticoagulants | Rattus norvegicus |
Y139C | naturally occuring mutant, resitant to warfarin and other anticoagulants | Rattus norvegicus |
Y139C | naturally occuring mutant, the mutant rat is resistant to some anticoagulants | Rattus norvegicus |
Y139F | naturally occuring mutant, resitant to warfarin and other anticoagulants | Rattus norvegicus |
Y139F | naturally occuring mutant, the mutant rat is resistant to some anticoagulants | Rattus norvegicus |
Y139S | naturally occuring mutant, resitant to warfarin and other anticoagulants | Rattus norvegicus |
Y139S | naturally occuring mutant, the mutant rat is resistant to some anticoagulants | Rattus norvegicus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
brodifacoum | non-competitive inhibition | Rattus norvegicus | |
bromadiolone | non-competitive inhibition | Rattus norvegicus | |
chlorophacinone | non-competitive inhibition | Rattus norvegicus | |
Difenacoum | non-competitive inhibition | Rattus norvegicus | |
difethialone | non-competitive inhibition | Rattus norvegicus | |
warfarin | non-competitive inhibition | Rattus norvegicus |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | reduction of vitamin K epoxide to vitamin K, Michaelis-Menten model, recombinant wild-type enzyme | Rattus norvegicus | |
additional information | - |
additional information | vitamin K 2,3-epoxid reduction kinetics, Michaelis-Menten model, overview | Rattus norvegicus | |
0.0072 | - |
2-methyl-3-phytyl-1,4-naphthoquinone | recombinant wild-type enzyme in recombinant Pichia pastoris membranes, pH 7.4, 37°C | Rattus norvegicus | |
0.0084 | - |
2-methyl-3-phytyl-1,4-naphthoquinone | native enzyme in membranes, pH 7.4, 37°C | Rattus norvegicus | |
0.0178 | - |
2-methyl-3-phytyl-1,4-naphthoquinone | mutant Y137F, pH 7.4, 37°C | Rattus norvegicus | |
0.0178 | - |
2,3-Epoxyphylloquinone | pH 7.4, 37°C, recombinant mutant Y139F enzyme | Rattus norvegicus | |
0.0195 | - |
2-methyl-3-phytyl-1,4-naphthoquinone | wild-type enzyme, pH 7.4, 37°C | Rattus norvegicus | |
0.0195 | - |
2,3-Epoxyphylloquinone | pH 7.4, 37°C, liver microsomes from rats homozygous for Y139F | Rattus norvegicus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
membrane | - |
Rattus norvegicus | 16020 | - |
microsome | - |
Rattus norvegicus | - |
- |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
2,3-epoxyphylloquinone + AH2 | Rattus norvegicus | the enzyme catalyzes the reduction of vitamin K 2,3-epoxide to vitamin K1, overview | phylloquinone + A + ? | - |
? | |
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O | Rattus norvegicus | reduction of vitamin K 2,3-epoxide to vitamin K | 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Rattus norvegicus | - |
gene VKORC1 | - |
Rattus norvegicus | Q6TEK4 | gene rVkorc1 | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
liver | - |
Rattus norvegicus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
2,3-epoxyphylloquinone + 1,4-dithiothreitol | - |
Rattus norvegicus | phylloquinone + oxidized dithiothreitol | - |
? | |
2,3-epoxyphylloquinone + AH2 | the enzyme catalyzes the reduction of vitamin K 2,3-epoxide to vitamin K1, overview | Rattus norvegicus | phylloquinone + A + ? | - |
? | |
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O | - |
Rattus norvegicus | 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol | - |
? | |
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O | reduction of vitamin K 2,3-epoxide to vitamin K | Rattus norvegicus | 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol | - |
? |
Synonyms | Comment | Organism |
---|---|---|
vitamin K epoxide reductase | - |
Rattus norvegicus |
VKORC1 | - |
Rattus norvegicus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Rattus norvegicus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Rattus norvegicus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
dithiothreitol | - |
Rattus norvegicus |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00005 | - |
difethialone | pH 7.4, 37°C, recombinant enzyme mutants Y139F, and L128Q | Rattus norvegicus | |
0.00006 | - |
brodifacoum | pH 7.4, 37°C, recombinant mutant Y139S enzyme | Rattus norvegicus | |
0.00007 | - |
Difenacoum | pH 7.4, 37°C, recombinant mutant L128Q enzyme | Rattus norvegicus | |
0.00007 | - |
brodifacoum | pH 7.4, 37°C, recombinant mutant Y139F enzyme | Rattus norvegicus | |
0.00008 | - |
brodifacoum | pH 7.4, 37°C, recombinant mutant L128Q enzyme | Rattus norvegicus | |
0.00009 | - |
brodifacoum | pH 7.4, 37°C, liver microsomes from rats homozygous for Y139F | Rattus norvegicus | |
0.00009 | - |
difethialone | pH 7.4, 37°C, liver microsomes from rats homozygous for Y139F | Rattus norvegicus | |
0.00009 | - |
Difenacoum | pH 7.4, 37°C, recombinant mutant Y139S enzyme | Rattus norvegicus | |
0.0001 | - |
difethialone | pH 7.4, 37°C, recombinant mutant Y139C enzyme | Rattus norvegicus | |
0.0001 | - |
Difenacoum | pH 7.4, 37°C, recombinant mutant Y139F enzyme | Rattus norvegicus | |
0.00011 | - |
brodifacoum | pH 7.4, 37°C, recombinant mutant Y139C enzyme | Rattus norvegicus | |
0.00011 | - |
difethialone | pH 7.4, 37°C, recombinant mutant Y139S enzyme | Rattus norvegicus | |
0.00016 | - |
difethialone | pH 7.4, 37°C, recombinant mutant L120Q enzyme | Rattus norvegicus | |
0.00016 | - |
Difenacoum | pH 7.4, 37°C, recombinant mutant Y139C enzyme | Rattus norvegicus | |
0.00018 | - |
bromadiolone | pH 7.4, 37°C, recombinant mutant L128Q enzyme | Rattus norvegicus | |
0.00018 | - |
chlorophacinone | pH 7.4, 37°C, recombinant mutant L128Q enzyme | Rattus norvegicus | |
0.00022 | - |
brodifacoum | pH 7.4, 37°C, recombinant mutant L120Q enzyme | Rattus norvegicus | |
0.00026 | - |
Difenacoum | pH 7.4, 37°C, liver microsomes from rats homozygous for Y139F | Rattus norvegicus | |
0.00049 | - |
bromadiolone | pH 7.4, 37°C, recombinant mutant Y139S enzyme | Rattus norvegicus | |
0.00051 | - |
bromadiolone | pH 7.4, 37°C, recombinant mutant L120Q enzyme | Rattus norvegicus | |
0.00061 | - |
bromadiolone | pH 7.4, 37°C, recombinant mutant Y139C enzyme | Rattus norvegicus | |
0.00069 | - |
bromadiolone | pH 7.4, 37°C, recombinant mutant Y139F enzyme | Rattus norvegicus | |
0.00089 | - |
Difenacoum | pH 7.4, 37°C, recombinant mutant L120Q enzyme | Rattus norvegicus | |
0.00091 | - |
bromadiolone | pH 7.4, 37°C, liver microsomes from rats homozygous for Y139F | Rattus norvegicus | |
0.0016 | - |
chlorophacinone | pH 7.4, 37°C, recombinant mutant Y139F enzyme, and liver microsomes from rats homozygous for Y139F | Rattus norvegicus | |
0.004 | - |
warfarin | pH 7.4, 37°C, recombinant mutant L128Q enzyme | Rattus norvegicus | |
0.0045 | - |
chlorophacinone | pH 7.4, 37°C, recombinant mutant L120Q enzyme | Rattus norvegicus | |
0.0073 | - |
chlorophacinone | pH 7.4, 37°C, recombinant mutant Y139C enzyme | Rattus norvegicus | |
0.0079 | - |
chlorophacinone | pH 7.4, 37°C, recombinant mutant Y139S enzyme | Rattus norvegicus | |
0.029 | - |
warfarin | pH 7.4, 37°C, liver microsomes from rats homozygous for Y139F | Rattus norvegicus | |
0.1 | - |
warfarin | above, pH 7.4, 37°C, recombinant enzyme mutants Y139F, L120Q, Y139C, Y139F, and Y139S | Rattus norvegicus |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00005 | - |
mutant Y137F, pH 7.4, 37°C | Rattus norvegicus | difethialone | |
0.00007 | - |
mutant Y137F, pH 7.4, 37°C | Rattus norvegicus | brodifacoum | |
0.00009 | - |
wild-type enzyme, pH 7.4, 37°C | Rattus norvegicus | brodifacoum | |
0.00009 | - |
wild-type enzyme, pH 7.4, 37°C | Rattus norvegicus | difethialone | |
0.0001 | - |
mutant Y137F, pH 7.4, 37°C | Rattus norvegicus | Difenacoum | |
0.00026 | - |
wild-type enzyme, pH 7.4, 37°C | Rattus norvegicus | Difenacoum | |
0.00061 | - |
mutant Y137F, pH 7.4, 37°C | Rattus norvegicus | bromadiolone | |
0.00091 | - |
wild-type enzyme, pH 7.4, 37°C | Rattus norvegicus | bromadiolone | |
0.0016 | - |
wild-type enzyme and mutant Y137F, pH 7.4, 37°C | Rattus norvegicus | chlorophacinone | |
0.029 | - |
wild-type enzyme, pH 7.4, 37°C | Rattus norvegicus | warfarin | |
0.1 | - |
above, mutant Y137F, pH 7.4, 37°C | Rattus norvegicus | warfarin |
General Information | Comment | Organism |
---|---|---|
malfunction | some naturally occuring mutations of the enzyme, e.g. at residues mutations at Leu120, Leu128 and Tyr139, confer resistance against anti-coagulants, sodium warfarin, difenacoum and brodifacoum, to rats | Rattus norvegicus |
additional information | compounds target blood coagulation by inhibiting the vitamin K epoxide reductase (VKORC1), which catalyzes the reduction of vitamin K 2,3-epoxide to vitamin K | Rattus norvegicus |
physiological function | function of VKORC1 is to regenerate vitamin K and vitamin K hydroquinone from vitamin K 2,3-epoxide, a byproduct of the vitamin K-dependent gamma carboxylation reaction | Rattus norvegicus |