Introduction

Figure 1. Closed Conformation of VKOR due to Warfarin Binding

Figure 2. Overview of Vitamin K Cycle

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

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).

[1]

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.

Cap Domain

Significant Cysteines

Vitamin K Epoxide

Warfarin