Sandbox Reserved 1725: Difference between revisions

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[https://en.wikipedia.org/wiki/Vitamin_K Vitamin K] is essential for [https://en.wikipedia.org/wiki/Coagulation#Coagulation_cascade blood clotting] in the body<ref name="Stafford">PMID:16102054</ref>. The fully reduced form, KH2, is used by [https://en.wikipedia.org/wiki/Gamma-glutamyl_carboxylase#:~:text=Gamma-glutamyl%20carboxylase%20is%20an%20enzyme%20that%20catalyzes%20the,of%20the%20encoded%20enzyme%20is%20essential%20for%20hemostasis gamma-glutamyl carboxylase] to carboxylate protein-bound glutamate residues in blood clotting cofactor precursors <ref name="Blanchard">PMID:6165889</ref>. After carboxylation, the clotting cofactors (such as [https://proteopedia.org/wiki/index.php/Thrombin prothrombin]) can bind to calcium and can proceed to the coagulation cascade <ref name="Swanson">PMID:6758841</ref>. During this process, KH2 becomes oxidized to Vitamin K epoxide, or KO <ref name="Blanchard">PMID:6165889</ref>. Vitamin K epoxide reductase, abbreviated VKOR, turns the epoxide back to the fully reduced form so the reduced form can be used again. This transformation happens in two steps: 1) converting the epoxide to the partially oxidized Vitamin K quinone and 2) converting the quinone to the fully reduced hydroquinone (KH2) (Figure 1) <ref name="Stafford">PMID:16102054</ref>.
[https://en.wikipedia.org/wiki/Vitamin_K Vitamin K] is essential for [https://en.wikipedia.org/wiki/Coagulation#Coagulation_cascade blood clotting] in the body<ref name="Stafford">PMID:16102054</ref>. The fully reduced form, KH2, is used by [https://en.wikipedia.org/wiki/Gamma-glutamyl_carboxylase#:~:text=Gamma-glutamyl%20carboxylase%20is%20an%20enzyme%20that%20catalyzes%20the,of%20the%20encoded%20enzyme%20is%20essential%20for%20hemostasis gamma-glutamyl carboxylase] to carboxylate protein-bound glutamate residues in blood clotting cofactor precursors <ref name="Blanchard">PMID:6165889</ref>. After carboxylation, the clotting cofactors (such as [https://proteopedia.org/wiki/index.php/Thrombin prothrombin]) can bind to calcium and can proceed to the coagulation cascade <ref name="Swanson">PMID:6758841</ref>. During this process, KH2 becomes oxidized to Vitamin K epoxide, or KO <ref name="Blanchard">PMID:6165889</ref>. Vitamin K epoxide reductase, abbreviated VKOR, turns the epoxide back to the fully reduced form so the reduced form can be used again. This transformation happens in two steps: 1) converting the epoxide to the partially oxidized Vitamin K quinone and 2) converting the quinone to the fully reduced hydroquinone (KH2) (Figure 1) <ref name="Stafford">PMID:16102054</ref>.


[[Image:vkor_crop.png|200 px|right|thumb|'''Figure 2. VKOR in Membrane''' The teal helices are the transmembrane helices. The tan sections are the beta loop and cap loop. The light blue section is the cap helix, and the dark blue section is the anchor. The cap loop, cap helix, and anchor make up the cap domain.]]
[[Image:vkor_crop.png|200 px|right|thumb|'''Figure 2. VKOR in Membrane''' Transmembrane helices are teal. The tan sections are the loops (loop 1, beta hairpin, cap loop, 3-4 loop). The cap helix is light blue and the anchor is dark blue.]]


=== Structural Overview ===
=== Structural Overview ===
VKOR consists of four <scene name='90/904330/Transmembranehelices1/5'>transmembrane helices</scene> embedded in the endoplasmic reticulum membrane. Helices one and two are connected by <scene name='90/904330/Betahairpin2/2'>Loop 1 and the beta hairpin</scene> region which contains two of the active cysteines, C43 and C51; these cysteines, along with C132 and C135, are essential for reduction and structural changes discussed in the next section<ref name="Liu">PMID:33154105</ref>. VKOR also has a <scene name='90/904330/Capdomain/1'>cap domain</scene> covering the active site, made up of an <scene name='90/904330/Capanchor/1'>anchor</scene>, <scene name='90/904330/Caploop/1'>loop</scene>, and <scene name='90/904330/Caphelix/1'>helix</scene>. The anchor serves to attach the cap domain to the ER membrane for stabilization<ref name="Liu">PMID:33154105</ref>. The loop helps stabilize one of the catalytic amino acids, Asn80<ref name="Liu">PMID:33154105</ref>. The helix is involved in stabilization of certain disulfide bonds and structural changes as part of the catalytic cycle discussed below<ref name="Liu">PMID:33154105</ref>.
VKOR consists of four <scene name='90/904330/Transmembranehelices1/5'>transmembrane helices</scene> embedded in the endoplasmic reticulum membrane. Helices one and two are connected by <scene name='90/904330/Betahairpin2/2'>Loop 1 and the beta hairpin</scene> region which contains two of the active cysteines, C43 and C51; these cysteines, along with C132 and C135, are essential for reduction and structural changes discussed in the next section<ref name="Liu">PMID:33154105</ref>. VKOR also has a cap domain consisting of a <b><span class="text-blue">helix</span></b>, <b><span class="text-green">loop</span></b>, and <b><span class="text-lightgreen">anchor</span></b>. The anchor serves to attach the cap domain to the ER membrane for stabilization<ref name="Liu">PMID:33154105</ref>. The loop helps stabilize one of the catalytic amino acids, Asn80<ref name="Liu">PMID:33154105</ref>. The helix is involved in stabilization of certain disulfide bonds and structural changes as part of the catalytic cycle discussed below<ref name="Liu">PMID:33154105</ref>.


=== Active Site ===
=== Active Site ===
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