Oxidoreductases;
Acting on CH or CH2 groups;
With a disulfide as acceptor

phylloquinone:disulfide oxidoreductase

(1) phylloquinone + a protein with a disulfide bond + H2O = 2,3-epoxyphylloquinone + a protein with reduced L-cysteine residues [RN:R03511];
(2) phylloquinol + a protein with a disulfide bond = phylloquinone + a protein with reduced L-cysteine residues

R03511;
(other) R03645 R09992

phylloquinone [CPD:C02059];
protein with a disulfide bond;
H2O [CPD:C00001];
phylloquinol [CPD:C03313]

The enzyme catalyses the reduction of vitamin K 2,3-epoxide, which is formed by the activity of EC 4.1.1.90, peptidyl-glutamate 4-carboxylase, back to its phylloquinol active form. The enzyme forms a tight complex with EC 5.3.4.1, protein disulfide-isomerase, which transfers the required electrons from newly-synthesized proteins by catalysing the formation of disulfide bridges. The enzyme acts on the epoxide forms of both phylloquinone (vitamin K1) and menaquinone (vitamin K2). Inhibited strongly by (S)-warfarin and ferulenol.

EC 1.17.4.4 created 1989 as EC 1.1.4.1, transferred 2014 to EC 1.17.4.4, modified 2018

1  [PMID:646989]

Whitlon DS, Sadowski JA, Suttie JW.

Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition.

Biochemistry 17:1371-7 (1978)

2  [PMID:6733086]

Lee JJ, Fasco MJ.

Metabolism of vitamin K and vitamin K 2,3-epoxide via interaction with a common disulfide.

Biochemistry 23:2246-52 (1984)

3  [PMID:3857611]

Mukharji I, Silverman RB.

Purification of a vitamin K epoxide reductase that catalyzes conversion of vitamin K 2,3-epoxide to 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone.

Proc Natl Acad Sci U S A 82:2713-7 (1985)
DOI:10.1073/pnas.82.9.2713

4  [PMID:14765195]

Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW

Identification of the gene for vitamin K epoxide reductase.

Nature 427:541-4 (2004)
DOI:10.1038/nature02254

5  [PMID:17124179]

Wajih N, Hutson SM, Wallin R

Disulfide-dependent protein folding is linked to operation of the vitamin K cycle in the endoplasmic reticulum. A protein disulfide isomerase-VKORC1 redox enzyme complex appears to be responsible for vitamin K1 2,3-epoxide reduction.

J Biol Chem 282:2626-35 (2007)
DOI:10.1074/jbc.M608954200

6  [PMID:19492146]

Spohn G, Kleinridders A, Wunderlich FT, Watzka M, Zaucke F, Blumbach K, Geisen C, Seifried E, Muller C, Paulsson M, Bruning JC, Oldenburg J

VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding.

Thromb Haemost 101:1044-50 (2009)

7  [PMID:20696932]

Schulman S, Wang B, Li W, Rapoport TA

Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners.

Proc Natl Acad Sci U S A 107:15027-32 (2010)
DOI:10.1073/pnas.1009972107