Sandbox Reserved 1724: Difference between revisions

[[Image:Vkor_cat_cycle_jpeg.jpg|400 px|right|thumb|'''Figure 3. Catalytic Cycle of VKOR''' VKOR's luminal domain is represented by a the pink semicircle and the transmembrane domain is represented by the gray cylinder. State I displays the fully oxidized VKOR in an open conformation. State II is a partially oxidized VKOR with free cysteines 43 and 135. State III is cysteine 135 interacting with KOH or KH to induce a closed conformation. State IV shows cysteine 132 attacking cysteine 135-KOH or KH to generate K.]]

The catalytic cycle of VKOR includes transitions from open to closed conformations by means of disulfide bridge-induced conformational changes (Figure 3). Open conformations of VKOR exist when there is no ligand within the binding pocket. Closed conformations exist when some substrate exists within the binding pocket of VKOR. The substituent cysteines (Fig 3, step I) act as reducing agents for the substrate, which can be either Vitamin K epoxide (KO) or partially reduced Vitamin K. The first step of the catalytic cycle (Figure 3) is the wild type open conformation, <scene name='90/904329/Cat_cycle_i/1'>step I</scene>. This step is characterized by an open cap domain with disulfide bonds between cysteines 43 and 51 and between cysteines 132 and 135  <ref name="Liu">PMID:33154105</ref>. The second step of the catalytic cycle is a partially oxidized open conformation, <scene name='90/904329/Cat_cycle_2/1'>step II</scene>. This step is characterized by a disulfide bond between the luminal and transmembrane domain (Fig 3, step II). The transmembrane domain contains a free Cys135 and the luminal domain contains a free Cys43 <ref name="Liu">PMID:33154105</ref>. Step II is labeled as open because no ligand exists within its binding pocket despite the disulfide bridge that connects the luminal and transmembrane domains. The next step of the cycle, <scene name='90/904329/Cat_cycle_3/5'>step III</scene>, is also a closed structure with an intact disulfide bond between Cys51 and Cys132. Cys135 is not involved in a disulfide bridge and assists with substrate binding by forming a stable adduct with KOH or K. This binding induces the closed conformation and uses Cys43 in the luminal membrane for electron transfer <ref name="Liu">PMID:33154105</ref>. <scene name='90/904329/Cat_cycle_4/1'>Step IV</scene> of the catalytic cycle is the last closed conformation. The Cys51-Cys132 bond is broken as Cys43 bonds with Cys51, recreating the disulfide bridge pattern of the open state. Cys132 is then free to bond with Cys135, releasing the product that was bound to the Cys135. Overall the catalytic cycle of VKOR is dependent on open and closed conformational changes of the protein and ultimately is used to generate vitamin K from vitamin K epoxide <ref name="Liu">PMID:33154105</ref>.