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Literature summary extracted from

  • Bevans, C.G.; Krettler, C.; Reinhart, C.; Tran, H.; Kossmann, K.; Watzka, M.; Oldenburg, J.
    Determination of the warfarin inhibition constant Ki for vitamin K 2,3-epoxide reductase complex subunit-1 (VKORC1) using an in vitro DTT-driven assay (2013), Biochim. Biophys. Acta, 1830, 4202-4210.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.17.4.4 expression in Pichia pastoris strain SMD 1168 Kex1- Homo sapiens
1.17.4.4 recombinant enzyme expression in Pichia pastoris strain SMD 1168 Kex1- endoplasmic reticulum membranes from a vector encoding (in 5'- to 3'-order): N-terminal alpha-mating factor from Saccharomyces cerevisiae, flag-tag epitope, His10-tag, Tev protease cleavage site, multiple cloning site, C-terminal Tev cleavage site, EGFP, Strep-tag II. The human VKORC1 DNA sequence is inserted into the multiple cloning site Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.17.4.4 warfarin direct inhibition Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.17.4.4 additional information
-
 additional information VKORC1 kinetic modeling, overview Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.17.4.4 membrane
-
 Homo sapiens 16020
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.17.4.4 Ca2+ Ca2+ might play a role in stabilizing the lipid membranes that surround the VKORC1 protein, but does not affect the DTT-driven enzyme activity Homo sapiens
1.17.4.4 additional information EGTA does not affect the DTT-driven enzyme activity Homo sapiens
1.17.4.4 additional information human VKOR enzymatic activity is not Ca2+-dependent, no effect by EGTA Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.17.4.4 2,3-epoxyphylloquinone + AH2 Homo sapiens
-
 phylloquinone + A + ?
-
 ?
1.17.4.4 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
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.17.4.4 Homo sapiens
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.17.4.4 phylloquinone + a protein with a disulfide bond + H2O = 2,3-epoxyphylloquinone + a protein with reduced L-cysteine residues bi bi ping-pong mechanism for VKORC1, kinetic modeling Homo sapiens
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.17.4.4 2,3-epoxyphylloquinone + 1,4-dithiothreitol
-
 Homo sapiens phylloquinone + oxidized dithiothreitol
-
 ?
1.17.4.4 2,3-epoxyphylloquinone + AH2
-
 Homo sapiens phylloquinone + A + ?
-
 ?
1.17.4.4 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
-
 ?
1.17.4.4 additional information advantages and caveats of using the DTT-driven VKOR assay, overview Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.17.4.4 vitamin K 2,3-epoxide reductase complex subunit-1
-
 Homo sapiens
1.17.4.4 VKORC1
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.17.4.4 30
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.17.4.4 6 7
-
 Homo sapiens
1.17.4.4 7.6
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.17.4.4 dithiothreitol
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.17.4.4 additional information
-
 additional information VKORC1 kinetic model and derivation of the IC50-Ki transformation, overview Homo sapiens
1.17.4.4 0.002633
-
 warfarin recombinant enzyme, pH 7.6, 30°C Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.17.4.4 0.00099
-
 at DTT concentration of over 1 mM, pH 7.6, 30°C Homo sapiens warfarin
1.17.4.4 0.00617
-
 at DTT concentration of 0.1123 mM, pH 7.6, 30°C Homo sapiens warfarin
1.17.4.4 0.02363
-
 at DTT concentration of 0.000296 mM, pH 7.6, 30°C Homo sapiens warfarin

General Information

EC Number General Information Comment Organism
1.17.4.4 physiological function vitamin K 2,3-epoxide reductase complex subunit 1 is an essential enzyme for proper function of blood coagulation Homo sapiens