%0 Book Section %T Human Vitamin K Epoxide Reductase as a Target of its Redox Protein %+ CB - Centre Borelli - UMR 9010 (CB) %A Ledoux, Julie %A Stolyarchuck, Maxim %A Tchertanov, Luba %B Book title Bioinformatics and Biomedical Engineering %E Ignacio Rojas %E Olga Valenzuela %E Fernando Rojas %E Luis Javier Herrera %E Francisco Ortuño %S https://link.springer.com/book/10.1007/978-3-031-07802-6 %V Lecture Notes in Computer Science (LNCS, volume 13347) %8 2022 %D 2022 %K hVKORC1 %K Trx-fold redox proteins • protein folding %K intrinsic disorder • modular protein • molecular recognition • thiol-disulphide exchange • protein-protein interactions • PDI-hVKORC1 complex • 3D modelling • molecular dynamics %Z Life Sciences [q-bio]Book sections %X 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. %G English %2 https://cnrs.hal.science/hal-03626866/document %2 https://cnrs.hal.science/hal-03626866/file/abstract_vkor_iwbbio2022.pdf %L hal-03626866 %U https://cnrs.hal.science/hal-03626866 %~ INSERM %~ SSA %~ CNRS %~ ENS-CACHAN %~ UNIV-PARIS-SACLAY %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SCIENCES %~ UNIVERSITE-PARIS-SACLAY %~ CGB %~ ENS-PARIS-SACLAY %~ ENS-PSACLAY %~ CB_UMR9010 %~ GS-MATHEMATIQUES