Three-dimensional and topology models of the vitamin K epoxide reductase. A) In silico 3D model of human vitamin K epoxide reductase based on the homologous bacterial protein structure (PDB-3KP9; ). The four transmembrane helices of the core protein are displayed in yellow, protein structures which are only present in the bacterial homolog (Trx-like domain, linker and 5th transmembrane domain) are shown in grey, imprecise regions in the human and bacterial protein structure are highlighted in red, positions of the 12 examined substitutions are represented in blue. The bound substrate (ubiquinone) is shown in white. The location of the interaction partner was verified for vitamin K1 within the human model using VINA  and found to be equivalent. B) Membrane topology model of the vitamin K epoxide reductase according to Li et al.  with the location of the 12 warfarin-resistant mutations examined in this study (red dots).