Sandbox Reserved 1709: Difference between revisions

<scene name='90/904314/Closed_conformation/6'>Text To Be Displayed</scene>=Vitamin K Epoxide Reductase=

<scene name='90/904314/Vkor_structure/1'>Vitamin K Epoxide Reductase</scene> (VKOR) is a reducing enzyme composed of 4-helices that spans the endoplasmic reticulum as a transmembrane protein<ref>DOI 10.1126/science.abc5667</ref>. Its enzymatic role is reducing <scene name='90/904314/Vkor_with_ko/7'>vitamin K epoxide</scene> (KO) to Vitamin K Hydroquinone (KH2)<ref>DOI 10.1021/bi700527j</ref> (Figure 1). The mechanism first occurs through the binding of KO and using two cysteine residues to reduce KO into [https://en.wikipedia.org/wiki/Vitamin_K Vitamin K]. Then, a second pair of cysteine residues will reduce Vitamin K into the final product, KH2 (Figure 1). One of VKOR's primary roles is to assist in blood coagulation through this KH2 regeneration mechanism.[[Image:VKOR_mechanism_2D.png|450 px|right|thumb|Figure 1. Mechanism of KO reduction into KH2.]] With Vitamin K as a cofactor, the [https://en.wikipedia.org/wiki/Gamma-glutamyl_carboxylase γ-carboxylase] enzyme will enact post-translational modification on KH2, oxidizing it back to KO <ref>DOI 10.1074/jbc.RA120.015401</ref>. The oxidation of KH2 by γ-carboxylase is coupled with the carboxylation of a glutamate residue to form γ-carboxyglutamate. The coupling of this oxidation and carboxylation will activate several clotting factors in the coagulation cascade.  

Mutations of the <scene name='90/906893/Vkor_with_warfarin_bound/4'>active site residues</scene> can occur within the binding pocket of VKOR. These mutations can be detrimental to the VKOR structure and function<ref>DOI 10.1126/science.abc5667</ref>. Two of the most common mutations occur to residues N80 and Y139 mutating them to <scene name='90/906893/Active_site_mutations/3'>A80 and F139</scene>. The change in polarity of these mutations from polar to nonpolar will cause a decrease in recognition and stabilization due to the inability to provide hydrogen bonds.