title: A hetero-dimer model for concerted action of vitamin K carboxylase and vitamin K reductase in vitamin K cycle.
abstract: Vitamin K carboxylase (VKC) is believed to convert vitamin K, in the vitamin K cycle, to an alkoxide-epoxide form which then reacts with CO(2) and glutamate to generate γ-carboxyglutamic acid (Gla). Subsequently, vitamin K epoxide reductase (VKOR) is thought to convert the alkoxide-epoxide to a hydroquinone form. By recycling vitamin K, the two integral-membrane proteins, VKC and VKOR, maintain vitamin K levels and sustain the blood coagulation cascade. Unfortunately, NMR or X-ray crystal structures of the two proteins have not been characterized. Thus, our understanding of the vitamin K cycle is only partial at the molecular level. In this study, based on prior biochemical experiments on VKC and VKOR, we propose a hetero-dimeric form of VKC and VKOR that may explain the efficient oxidation and reduction of vitamin K during the vitamin K cycle.
authors: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, USA.
authors: Sangwook
authors: S
authors: Wu
authors: Shubin
authors: S
authors: Liu
authors: Charles H
authors: CH
authors: Davis
authors: Darrel W
authors: DW
authors: Stafford
authors: John D
authors: JD
authors: Kulman
authors: Lee G
authors: LG
authors: Pedersen
mesh_terms: D019735:Carbon-Carbon Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D014812:Vitamin K / Q000378:metabolism*; D014859:Warfarin / Q000494:pharmacology
chemical_list: D014812:Vitamin K; D014859:Warfarin; D016660:NAD(P)H Dehydrogenase (Quinone); D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase