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Literature summary for 1.17.4.4 extracted from

  • Fregin, A.; Czogalla, K.J.; Gansler, J.; Rost, S.; Taverna, M.; Watzka, M.; Bevans, C.G.; Mueller, C.R.; Oldenburg, J.
    A new cell culture-based assay quantifies vitamin K 2,3-epoxide reductase complex subunit 1 function and reveals warfarin resistance phenotypes not shown by the dithiothreitol-driven VKOR assay (2013), J. Thromb. Haemost., 11, 872-880.
    View publication on PubMed
Search for more literature for 1.17.4.4

Cloned(Commentary)

Cloned (Comment) Organism
coexpression of human coagulation factor (F)IX and c-myc-tagged VKORC1 mutant variants in HEK-293T cells in presence of varying warfarin concentrations Homo sapiens
coexpression of human coagulation factor (F)IX andc-myc-tagged VKORC1 wild-type and mutants in HEK-293T cells in presence of varying warfarin concentrations Homo sapiens

Protein Variants

Protein Variants Comment Organism
L128R site-directed mutagenesis, the mutant is resistant to warfarin and oral anti-coagulants Homo sapiens
additional information construction of warfarin-resistant VKORC1 variants following naturally occuring mutations in patients Homo sapiens
V29L site-directed mutagenesis, the mutant is resistant to warfarin and oral anti-coagulants Homo sapiens
V45A site-directed mutagenesis, the mutant is resistant to warfarin and oral anti-coagulants Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
warfarin mutants V29L, V45A, and L128R are resistant to inhibition by warfarin in vivo, oveview; VKORC1 function is measured in vitro using a dithiothreitol-driven vitamin K 2,3-epoxide reductase assay. Warfarin inhibits wild-type VKORC1 function by the DTT–VKOR assay. However, VKORC1 variants with warfarin resistance-associated missense mutations often show low VKOR activities and warfarin sensitivity instead of resistance Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O Homo sapiens
-
 2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
 ?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O Homo sapiens
-
 2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
 r
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
-
 ?
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

Organism UniProt Comment Textmining
Homo sapiens Q9BQB6
-
-
Homo sapiens Q9BQB6 mutants V29L, V45A, and L128R, oveview
-

Source Tissue

Source Tissue Comment Organism Textmining
HEK-293T cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
-
 Homo sapiens 2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
 ?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
-
 Homo sapiens 2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
 r
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
-
 ?
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

Synonyms

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

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
additional information
-
 IC50 values for warfarin determined by different assay methods, overview Homo sapiens additional information
0.0000247
-
 pH and temperature not specified in the publication Homo sapiens warfarin
0.000136
-
 mutant V129L, pH and temperature not specified in the publication Homo sapiens warfarin
0.000152
-
 mutant V145A, pH and temperature not specified in the publication Homo sapiens warfarin
0.001226
-
 mutant L128R, pH and temperature not specified in the publication Homo sapiens warfarin

General Information

General Information Comment Organism
additional information VKORC1 function is measured in vitro using a dithiothreitol-driven vitamin K 2,3-epoxide reductase assay. Warfarin inhibits wild-type VKORC1 function by the DTT-VKOR assay. However, VKORC1 variants with warfarin resistance-associated missense mutations often show low VKOR activities and warfarin sensitivity instead of resistance. Development and evaluation of a cell culture-based, indirect VKOR assay accurately reports warfarin sensitivity or resistance for wild-type and variant VKORC1 proteins Homo sapiens
additional information VKORC1 function is measured in vitro using a dithiothreitol-driven vitamin K 2,3-epoxide reductase assay. Warfarin inhibits wild-type VKORC1 function by the DTT–VKOR assay. However, VKORC1 variants with warfarin resistance-associated missense mutations often show low VKOR activities and warfarin sensitivity instead of resistance. Development and evaluation of a cell culture-based, indirect VKOR assay accurately reports warfarin sensitivity or resistance for wild-type and variant VKORC1 proteins Homo sapiens