The recent crystal structure of human-VKORC1 complexes with Vitamin K and/or anticoagulants, including brodifacoum (Figure ) suggested that oxidized Vitamin K binds to the top of the VKORC1 cavity causing an open-toclose Cys51 conformational change that triggers oxred reactions . The top cavity contains Cys132, Cys135, and the binding-sites for the heads of Vitamin K and/or anticoagulants (coumarin/indandione). The VKORC1 binding is stabilized by interactions down into the central cavity of the hydrophobic tails of Vitamin K and/or other anticoagulants including hydrogen bonds to residues Asn80 and Tyr139. Binding induces also the displacement of the Cys43-Cys 51 disulphide bond to the top cavity facilitating interchange of reductions of Cys132/Cys135 and oxidized Vitamin K. After reduction, the top cavity opens up facilitating the exclusion of re-activated Vitamin K to continue with other carboxylation cycle. Actual anticoagulant rodenticides target VKORC1 by mimicking Vitamin K binding at similar binding-cavities and conformational changes.