Cloned (Comment) | Organism |
---|---|
gene Vkorc1, expression of wild-type and mutant enzymes in Pichia pastoris as membrane bound protein | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
L120Q | naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, no synthesis of no 2-OH-vitamin K1 or 3-OH-vitamin K1 | Homo sapiens |
L128Q | naturally occuring mutation, no synthesis of no 2-OH-vitamin K1 or 3-OH-vitamin K1 | Homo sapiens |
Y139C | naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, additional synthesis of 3-hydroxyvitamin K1 | Homo sapiens |
Y139C | site-directed mutagenesis, the mutation dramatically affects the vitamin K epoxide reductase activity | Homo sapiens |
Y139F | naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, additional synthesis of 3-hydroxyvitamin K1 | Homo sapiens |
Y139S | naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, additional synthesis of 3-hydroxyvitamin K1 | Homo sapiens |
Y139S | site-directed mutagenesis, the mutation dramatically affects the vitamin K epoxide reductase activity, additional production of 3-hydroxyvitamin K1 in the mutant | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
Difenacoum | non-competitive inhibition | Homo sapiens | |
warfarin | - |
Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0072 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, wild-type enzyme | Homo sapiens | |
0.012 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, mutant L128Q | Homo sapiens | |
0.013 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, mutant Y139S | Homo sapiens | |
0.018 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, mutant Y139F | Homo sapiens | |
0.025 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, mutant L120Q | Homo sapiens | |
0.06 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, mutant Y139C | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
microsome | - |
Homo sapiens | - |
- |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O | Homo sapiens | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
gene VKORC1 | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
liver | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O | - |
Homo sapiens | 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol | - |
r | |
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O | crucial role of the Tyr-139 amino acid in this reaction mechanism, Tyr-139 residue appears to determine the second half-step of the catalytic mechanism | Homo sapiens | 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol | - |
r | |
additional information | no synthesis of 3-hydroxyvitamin K1 by the wild-type enzyme, but by mutants Y139C, Y139F, and Y139S | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
vitamin K epoxide reductase | - |
Homo sapiens |
VKORC1 | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0072 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, wild-type enzyme | Homo sapiens | |
0.012 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, mutant L128Q | Homo sapiens | |
0.013 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, mutant Y139S | Homo sapiens | |
0.018 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, mutant Y139F | Homo sapiens | |
0.025 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, mutant L120Q | Homo sapiens | |
0.06 | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone | pH 7.4, 37°C, mutant Y139C | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Homo sapiens |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00003 | - |
Difenacoum | wild-typpe enzyme, pH 7.4, 37°C | Homo sapiens | |
0.00007 | - |
Difenacoum | mutant L128Q, pH 7.4, 37°C | Homo sapiens | |
0.00009 | - |
Difenacoum | mutant Y139S, pH 7.4, 37°C | Homo sapiens | |
0.0001 | - |
Difenacoum | mutant Y139F, pH 7.4, 37°C | Homo sapiens | |
0.00016 | - |
Difenacoum | mutant Y139C, pH 7.4, 37°C | Homo sapiens | |
0.0005 | - |
warfarin | wild-typpe enzyme, pH 7.4, 37°C | Homo sapiens | |
0.00089 | - |
Difenacoum | mutant L120Q, pH 7.4, 37°C | Homo sapiens | |
0.004 | - |
warfarin | mutant L128Q, pH 7.4, 37°C | Homo sapiens |