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Literature summary for 1.17.4.4 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

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

Cloned(Commentary)

Cloned (Comment) Organism
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

Protein Variants Comment Organism
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
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

Localization Comment Organism GeneOntology No. Textmining
membrane VKOR is an integral membrane protein Homo sapiens 16020
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
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

Organism UniProt Comment Textmining
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 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 + ?
-
?
2,3-epoxyphylloquinone + reduced thioredoxin
-
Homo sapiens phylloquinone + oxidized thioredoxin
-
?

Synonyms

Synonyms Comment Organism
vitamin K oxidoreductase
-
Homo sapiens
VKOR
-
Homo sapiens

Temperature Optimum [°C]

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

pH Optimum

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

General Information

General Information Comment Organism
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
physiological function the vitamin K oxidoreductase reduces vitamin K to support the carboxylation and consequent activation of vitamin K-dependent proteins Homo sapiens