Synergy of Mutation-Induced Effects in Human Vitamin K Epoxide Reductase: Perspectives and Challenges for Allo-Network Modulator Design.

ABSTRACT: The human Vitamin K Epoxide Reductase Complex (hVKORC1), a key enzyme transforming vitamin K into the form necessary for blood clotting, requires for its activation the reducing equivalents delivered by its redox partner through thiol-disulfide exchange reactions. The luminal loop (L-loop) is the principal mediator of hVKORC1 activation, and it is a region frequently harbouring numerous missense mutations. Four L-loop hVKORC1 mutants, suggested in vitro as either resistant (A41S, H68Y) or completely inactive (S52W, W59R), were studied in the oxidised state by numerical approaches (in silico). The DYNASOME and POCKETOME of each mutant were characterised and compared to the native protein, recently described as a modular protein composed of the structurally stable transmembrane domain (TMD)

SUBMITTER: Botnari M 

PROVIDER: S-EPMC10889538 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature