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Human Vitamin K Epoxide Reductase as a Target of its Redox Protein


Human Vitamin K epoxide reductase (hVKORC1) is a key enzyme to reduce vitamin K. Such function requires activation of the enzyme by a redox partner delivering reducing equivalents through thioldisulphide exchange reactions. The activation process represents a first and less studied step in hVKORC1 vital cycle, involving the oxidised luminal loop (L-loop) and a reduced thioredoxin protein (Trx), which is yet undefined for hVKORC1. A careful in silico study, based on molecular dynamic (MD) simulations of hVKORC1 in oxidised state, and a comparative analysis of four Trx proteins-protein disulphide isomerase (PDI), endoplasmic reticulum oxidoreductase (ERp18), thioredoxin-related transmembrane protein 1 (Tmx1) and thioredoxin-related transmembrane protein 4 (Tmx4)), viewed as the most probable reducers of hVKORC1-in their sequence, secondary and tertiary structure, dynamics, intraprotein interactions and composition of the surface exposed to the target-provided the identification of putative recognition/binding sites on each isolated protein. PDI was suggested as the most probable hVKORC1 partner. By probing the alternative orientation of PDI with respect to hVKORC1, two PDI-VKOR models were proposed and one of them considered as precursor for thiol-disulphide exchange reactions.
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hal-03626866 , version 1 (31-03-2022)


  • HAL Id : hal-03626866 , version 1


Julie Ledoux, Maxim Stolyarchuck, Luba Tchertanov. Human Vitamin K Epoxide Reductase as a Target of its Redox Protein. Ignacio Rojas, Olga Valenzuela, Fernando Rojas, Luis Javier Herrera, Francisco Ortuño. Book title Bioinformatics and Biomedical Engineering, Lecture Notes in Computer Science (LNCS, volume 13347), 2022, ⟨hal-03626866⟩
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