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As mentioned above, Vitamin K epoxide is a part of the Vitamin K cycle, necessary for blood coagulation. In the cycle, Vitamin K epoxide reductase (VKOR) reduces Vitamin K epoxide to quinone, or the active form of Vitamin K. What is occurring is VKOR donated electrons to Vitamin K epoxide, and those electrons come from the S-H of one of the cysteine pairs discussed above. The one cysteine pair has to be reduced for the transfer of electrons to the substrate can occur.
As mentioned above, Vitamin K epoxide is a part of the Vitamin K cycle, necessary for blood coagulation. In the cycle, Vitamin K epoxide reductase (VKOR) reduces Vitamin K epoxide to quinone, or the active form of Vitamin K. What is occurring is VKOR donated electrons to Vitamin K epoxide, and those electrons come from the S-H of one of the cysteine pairs discussed above. The one cysteine pair has to be reduced for the transfer of electrons to the substrate can occur.
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Two other notable structures are Vitamin K Quinone and Vitamin K Hydroquinone. Vitamin K Quinone is the product that is released after the reaction with Vitamin K Epoxide and VKOR. (Fig. 2)
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[[Image:Vitaminkquinone.png|200 px|left|thumb|Figure 5. Vitamin K Quinone structure]] [[Image:Vitaminkhydroquinone|200 px|right|thumb|Figure 6. Vitamin K Hydroquinone structure]]
=== Binding ===
=== Binding ===
To start, VKOR is in its <scene name='90/904322/Open_conformation/1'>open conformation</scene>. The Vitamin K epoxide enters through the isoprenyl- chain tunnel. The oxygens of the ketones bind to <scene name='90/904322/Vko_binding/1'>Asn80 and Tyr139</scene>. With Vitamin K epoxide in its place, the conformation of VKOR is partially oxidized in regards to the cysteine pairs, which overall leads to the reduction of the substrate. A disulfide bond forms between Cys51 and Cys132, resulting in the closed conformation. This leaves the sulfur on Cys43 and the sulfur on Cys135 protonated. The available hydrogens on these cysteines are utilized in reducing the epoxide. First, the sulfur on Cys51 and Cys43 form a new bond. The hydrogen from Cys43 binds to the oxygen in the epoxide. The sulfur on Cys132 and the sulfur on Cys135 then form a new disulfide bond. The hydrogen that was present on Cys135 forms a new bond with the oxygen of the epoxide. With these cysteine pairs formed, VKOR is left in an open conformation. The end products are the Vitamin K/quinone and water.
To start, VKOR is in its <scene name='90/904322/Open_conformation/1'>open conformation</scene>. The Vitamin K epoxide enters through the isoprenyl- chain tunnel. The oxygens of the ketones bind to <scene name='90/904322/Vko_binding/1'>Asn80 and Tyr139</scene>. With Vitamin K epoxide in its place, the conformation of VKOR is partially oxidized in regards to the cysteine pairs, which overall leads to the reduction of the substrate. A disulfide bond forms between Cys51 and Cys132, resulting in the closed conformation. This leaves the sulfur on Cys43 and the sulfur on Cys135 protonated. The available hydrogens on these cysteines are utilized in reducing the epoxide. First, the sulfur on Cys51 and Cys43 form a new bond. The hydrogen from Cys43 binds to the oxygen in the epoxide. The sulfur on Cys132 and the sulfur on Cys135 then form a new disulfide bond. The hydrogen that was present on Cys135 forms a new bond with the oxygen of the epoxide. With these cysteine pairs formed, VKOR is left in an open conformation. The end products are the Vitamin K/quinone and water.
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== Warfarin ==
== Warfarin ==
[https://en.wikipedia.org/wiki/Warfarin Warfarin] is the most common [https://en.wikipedia.org/wiki/Vitamin_K_antagonist Vitamin K antagonist (VKA)]. Warfarin is a competitive inhibitor, taking the place of Vitamin K Epoxide (VKO) in the active site of Vitamin K Epoxide Reductase (VKOR). When warfarin binds in the active site, it causes VKOR to go into the closed conformation.
[https://en.wikipedia.org/wiki/Warfarin Warfarin] is the most common [https://en.wikipedia.org/wiki/Vitamin_K_antagonist Vitamin K antagonist (VKA)]. Warfarin is a competitive inhibitor, taking the place of Vitamin K Epoxide (VKO) in the active site of Vitamin K Epoxide Reductase (VKOR). When warfarin binds in the active site, it causes VKOR to go into the closed conformation.
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[[Image:warfarin.jpg|400 px|right|thumb|Figure 5. 2-Dimensional structure of Warfarin]]
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[[Image:warfarin.jpg|400 px|right|thumb|Figure 7. 2-Dimensional structure of Warfarin]]
=== Binding ===
=== Binding ===

Revision as of 18:51, 5 April 2022

Vitamin K Epoxide Reductase

Structure of Closed Vitamin K Epoxide Reductase (PDB entry 6wv3)

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