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Literature summary for 1.17.4.4 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)

Cloned (Comment) Organism
expression in Pichia pastoris strain SMD 1168 Kex1- Homo sapiens
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

Inhibitors Comment Organism Structure
warfarin direct inhibition Homo sapiens

KM Value [mM]

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

Localization

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

Metals/Ions

Metals/Ions Comment Organism Structure
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
additional information EGTA does not affect the DTT-driven enzyme activity Homo sapiens
additional information human VKOR enzymatic activity is not Ca2+-dependent, no effect by EGTA Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Reaction

Reaction Comment Organism Reaction ID
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

Substrates and Products (Substrate)

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

Synonyms

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

Temperature Optimum [°C]

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

pH Optimum

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

Cofactor

Cofactor Comment Organism Structure
dithiothreitol
-
Homo sapiens

Ki Value [mM]

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

IC50 Value

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

General Information

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