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Literature summary extracted from

  • Rishavy, M.A.; Usubalieva, A.; Hallgren, K.W.; Berkner, K.L.
    Novel insight into the mechanism of the vitamin K oxidoreductase (VKOR): electron relay through Cys43 and Cys51 reduces VKOR to allow vitamin K reduction and facilitation of vitamin K-dependent protein carboxylation (2011), J. Biol. Chem., 286, 7267-7278.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.17.4.4 DTT activation in intact and Cys-mutated membranes Homo sapiens
1.17.4.4 thioredoxin activation only in intact membranes Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.17.4.4 expression in Spodoptera frugiperda Sf21 cell microsomes using baculovirus containing wild-type or mutant VKORs transfection method, in vitro transcription and translation of the human enzyme using r-VKORC1/ZEM229 as the template Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.17.4.4 C43A site-directed mutagenesis, the mutant shows vitamin K epoxide reduction activity similar to the wild-type enzyme, but only with the membrane-permeant reductant DTT, no mutant activity with thioredoxin as reductant Homo sapiens
1.17.4.4 C51A site-directed mutagenesis, the mutant shows vitamin K epoxide reduction activity similar to the wild-type enzyme, but only with the membrane-permeant reductant DTT, no mutant activity with thioredoxin as reductant Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.17.4.4 membrane VKOR is an integral membrane protein Homo sapiens 16020
-
4.1.1.90 endoplasmic reticulum
-
 Homo sapiens 5783
-

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 VKOR reduces vitamin K using membrane-embedded thiols, Cys132 and Cys135, which become oxidized with concomitant VKOR inactivation. VKOR is subsequently reactivated by an unknown redox protein that might act directly on the Cys132-Cys135 residues phylloquinone + A + ?
-
 ?

Organism

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

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 VKOR reduces vitamin K using membrane-embedded thiols, Cys132 and Cys135, which become oxidized with concomitant VKOR inactivation. VKOR is subsequently reactivated by an unknown redox protein that might act directly on the Cys132-Cys135 residues Homo sapiens phylloquinone + A + ?
-
 ?
1.17.4.4 2,3-epoxyphylloquinone + reduced thioredoxin
-
 Homo sapiens phylloquinone + oxidized thioredoxin
-
 ?
4.1.1.90 L-glutamate + CO2 + O2 + vitamin K hydroquinone the enzyme uses oxygenation of vitamin K hydroquinone to vitamin K epoxide to drive the incorporation of CO2 into glutamyl residues to produce carboxylated glutamate in vitamin K-dependent proteins Homo sapiens gamma-carboxy L-glutamate + vitamin K epoxide + H2O
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.17.4.4 vitamin K oxidoreductase
-
 Homo sapiens
1.17.4.4 VKOR
-
 Homo sapiens
4.1.1.90 gamma-glutamyl carboxylase
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.17.4.4 21
-
 assay at Homo sapiens

pH Optimum

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

Cofactor

EC Number Cofactor Comment Organism Structure
4.1.1.90 vitamin K
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
1.17.4.4 additional information role for Cys43 and Cys51 in catalysis with a relay mechanism in which a redox protein transfers electrons to these loop residues, which in turn reduce the membrane-embedded Cys132-Cys135 disulfide bond to activate VKOR Homo sapiens
1.17.4.4 physiological function the vitamin K oxidoreductase reduces vitamin K to support the carboxylation and consequent activation of vitamin K-dependent proteins Homo sapiens