InterPro domain: IPR044698

Proteins containing this domain (also known as VKOR domain) are from bacteria, plants and archaea. They are homologous to mammalian Vitamin K epoxide reductases (VKORC1). In some plant and bacterial homologues, the VKOR domain is fused with domains of the thioredoxin family of oxidoreductases which may function as redox partners in initiating the reduction cascade [ 1 ]. Proteins containing this domain include Thiol-disulfide oxidoreductase LTO1 (also known as Vitamin K reductase, AtVKOR) from Arabidopsis [ 2 ] and Vitamin K epoxide reductase homologue (VKOR) from Synechococcus sp. [ 3 , 4 ]. In general, they disulfide bond–forming enzymes which control disulfide bond formation [ 5 ]. All homologues of VKOR contain an active site CXXC motif, which is switched between reduced and disulfide-bonded states during the reaction cycle [ 5 ].

In Arabidopsis LTO1 catalyses disulfide bond formation of chloroplast proteins and is involved in thylakoid redox regulation and photosynthetic electron transport [ 6 ]. It is required for the assembly of photosystem II (PSII) through the formation of disulfide bond in PSBO, a subunit of the PSII oxygen-evolving complex in the thylakoid lumen [ 7 ]. Bacterial VKOR homologues catalyse disulphide bridge formation in secreted proteins by cooperating with a periplasmic, Trx-like redox partner [ 7 , 8 ].

1. Vitamin K epoxide reductase: homology, active site and catalytic mechanism. Trends Biochem. Sci. 29, 289-92
2. Lumen Thiol Oxidoreductase1, a disulfide bond-forming catalyst, is required for the assembly of photosystem II in Arabidopsis. Plant Cell 23, 4462-75
3. Structure of a bacterial homologue of vitamin K epoxide reductase. Nature 463, 507-12
4. Structures of an intramembrane vitamin K epoxide reductase homolog reveal control mechanisms for electron transfer. Nat Commun 5, 3110
5. The vitamin K cycle. Vitam. Horm. 78, 35-62
6. Identification of potential targets for thylakoid oxidoreductase AtVKOR/LTO1 in chloroplasts. Protein Pept. Lett. 22, 219-25
7. Identification of an atypical membrane protein involved in the formation of protein disulfide bonds in oxygenic photosynthetic organisms. J. Biol. Chem. 283, 15762-70
8. Bacterial species exhibit diversity in their mechanisms and capacity for protein disulfide bond formation. Proc. Natl. Acad. Sci. U.S.A. 105, 11933-8