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Literature summary extracted from

  • Matagrin, B.; Hodroge, A.; Montagut-Romans, A.; Andru, J.; Fourel, I.; Besse, S.; Benoit, E.; Lattard, V.
    New insights into the catalytic mechanism of vitamin K epoxide reductase (VKORC1) - The catalytic properties of the major mutations of rVKORC1 explain the biological cost associated to mutations (2013), FEBS Open Bio, 3, 144-150.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.17.4.4 gene Vkorc1, expression of wild-type and mutant enzymes in Pichia pastoris as membrane bound protein Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.17.4.4 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
1.17.4.4 L128Q naturally occuring mutation, no synthesis of no 2-OH-vitamin K1 or 3-OH-vitamin K1 Homo sapiens
1.17.4.4 Y139C naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, additional synthesis of 3-hydroxyvitamin K1 Homo sapiens
1.17.4.4 Y139C site-directed mutagenesis, the mutation dramatically affects the vitamin K epoxide reductase activity Homo sapiens
1.17.4.4 Y139F naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, additional synthesis of 3-hydroxyvitamin K1 Homo sapiens
1.17.4.4 Y139S naturally occuring mutation, the mutant is resistant to warfarin, but not to difenacoum, additional synthesis of 3-hydroxyvitamin K1 Homo sapiens
1.17.4.4 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

EC Number Inhibitors Comment Organism Structure
1.17.4.4 Difenacoum non-competitive inhibition Homo sapiens
1.17.4.4 warfarin
-
 Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.17.4.4 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
1.17.4.4 0.012
-
 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone pH 7.4, 37°C, mutant L128Q Homo sapiens
1.17.4.4 0.013
-
 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone pH 7.4, 37°C, mutant Y139S Homo sapiens
1.17.4.4 0.018
-
 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone pH 7.4, 37°C, mutant Y139F Homo sapiens
1.17.4.4 0.025
-
 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone pH 7.4, 37°C, mutant L120Q Homo sapiens
1.17.4.4 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

EC Number Localization Comment Organism GeneOntology No. Textmining
1.17.4.4 microsome
-
 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-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

EC Number Organism UniProt Comment Textmining
1.17.4.4 Homo sapiens
-
 gene VKORC1
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.17.4.4 liver
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
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
-
 r
1.17.4.4 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
1.17.4.4 additional information no synthesis of 3-hydroxyvitamin K1 by the wild-type enzyme, but by mutants Y139C, Y139F, and Y139S Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.17.4.4 vitamin K epoxide reductase
-
 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 37
-
 assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.17.4.4 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
1.17.4.4 0.012
-
 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone pH 7.4, 37°C, mutant L128Q Homo sapiens
1.17.4.4 0.013
-
 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone pH 7.4, 37°C, mutant Y139S Homo sapiens
1.17.4.4 0.018
-
 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone pH 7.4, 37°C, mutant Y139F Homo sapiens
1.17.4.4 0.025
-
 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone pH 7.4, 37°C, mutant L120Q Homo sapiens
1.17.4.4 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

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.17.4.4 7.4
-
 assay at Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.17.4.4 0.00003
-
 Difenacoum wild-typpe enzyme, pH 7.4, 37°C Homo sapiens
1.17.4.4 0.00007
-
 Difenacoum mutant L128Q, pH 7.4, 37°C Homo sapiens
1.17.4.4 0.00009
-
 Difenacoum mutant Y139S, pH 7.4, 37°C Homo sapiens
1.17.4.4 0.0001
-
 Difenacoum mutant Y139F, pH 7.4, 37°C Homo sapiens
1.17.4.4 0.00016
-
 Difenacoum mutant Y139C, pH 7.4, 37°C Homo sapiens
1.17.4.4 0.0005
-
 warfarin wild-typpe enzyme, pH 7.4, 37°C Homo sapiens
1.17.4.4 0.00089
-
 Difenacoum mutant L120Q, pH 7.4, 37°C Homo sapiens
1.17.4.4 0.004
-
 warfarin mutant L128Q, pH 7.4, 37°C Homo sapiens