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Vitamin K Epoxide Reductase

spinqualitylabelsall models Structure of Closed Vitamin K Epoxide Reductase (PDB entry 6wv3) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Figure 1. Closed Conformation of VKOR due to Warfarin Binding Introduction Figure 2. Overview of Vitamin K Cycle Vitamin K Epoxide Reductase (VKOR) is an endoplasmic membrane enzyme that generates the active form of Vitamin K to support blood coagulation. The vitamin K Cycle, and the VKOR enzyme specifically are common drug targets for thromboembolic diseases. This is because, as pictured, the vitamin K cycle is the process in which blood coagulant factors II, VII, IX, and X are activated. This promotes blood clotting, which can be dangerous and cause thromboembolic diseases such as stroke, deep vein thrombosis, and/or pulmonary embolism. Location of Enzyme Vitamin K Epoxide Reductase is found and primarily synthesized in the liver. It is embedded in the membrane known as the endoplasmic reticulum. Structure Spinning VKOR VKOR WIKI The VKOR enzyme is made up of four transmembrane helices: T1, T2, T3, and T4.(Grey) Each of these helices come together to form a hydrophobic pocket, that is topped by a cap domain. In the cap domain are important regions that are significant for Vitamin K binding, and the overall function of Vitamin K Epoxide Reductase. These important regions are the Anchor(Green), Cap Region (Blue), Beta Hairpin (Purple), and 3-4 Loop (Pink). Transmembrane Helices The Transmembrane helices are named Transmembrane Helix 1, Transmembrane Helix 2, Transmembrane Helix 3, and Transmembrane Helix 4. The residues on Transmembrane Helix 2 (TM2) and Transmembrane Helix 4 (TM4) are significant for the binding of Vitamin K to the hydrophobic pocket of the enzyme. Asparagine 222 (make sure this is right) on TM2 and Tyrosine 281(make sure this is right) hydrogen bond to Vitamin K Epoxide, in order to hold it in place so that it may be reduced. Cysteine residues from the cap domain will donate their electrons to Vitamin K Epoxide to open the epoxide ring, and reform Vitamin K Quinone. Significant Cysteines Cysteine 43 and 51 and Residues in Between Warfarin Warfarin Binding