Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 1.17.4.4 extracted from

  • Hodroge, A.; Longin-Sauvageon, C.; Fourel, I.; Benoit, E.; Lattard, V.
    Biochemical characterization of spontaneous mutants of rat VKORC1 involved in the resistance to antivitamin K anticoagulants (2011), Arch. Biochem. Biophys., 515, 14-20.
    View publication on PubMed
Search for more literature for 1.17.4.4

Cloned(Commentary)

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

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

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 [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

Localization Comment Organism GeneOntology No. Textmining
membrane
-
 Rattus norvegicus 16020
-
microsome
-
 Rattus norvegicus
-
-

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Rattus norvegicus
-
 gene VKORC1
-
Rattus norvegicus Q6TEK4 gene rVkorc1
-

Source Tissue

Source Tissue Comment Organism Textmining
liver
-
 Rattus norvegicus
-

Substrates and Products (Substrate)

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

Synonyms Comment Organism
vitamin K epoxide reductase
-
 Rattus norvegicus
VKORC1
-
 Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Rattus norvegicus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Rattus norvegicus

Cofactor

Cofactor Comment Organism Structure
dithiothreitol
-
 Rattus norvegicus

Ki Value [mM]

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 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

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