Sandbox Reserved 1724: Difference between revisions

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===Overview===
===Overview===
 
The catalytic cycle shows how vitamin K epoxide reductase structurally transforms from an open wild type conformation to having several different types of substrates within its binding pocket. The first step of the catalytic cycle of shown to the right is the wild type open conformation, labeled I. This step is characterized by an open cap domain with a disulfide bond (43-51) and a second disulfide bond (132-135) in the alpha helices. As shown this step can be characterized as closed when warfarin sits within the binding pocket without the disulfide bonds changing so that the cap domain does not actually close. This step is considered closed because vitamin K would not be able to enter the binding pocket in any of its forms. The second step of the catalytic cycle is a closed conformation labeled II. This step is characterized by a disulfide bond between the cap domain and alpha helices, with both containing an SH group. Warfarin can sit within this structure without disrupting and of these sulfur groups. The next step of the cycle, labeled III, is slightly different because KOH or KH (depending on the step of the vitamin K cycle) binds to the cysteine 135 within the alpha helices. This is also a closed structure. Lastly, structure IV of the catalytic cycle is also a closed structure. The major difference is the orientation of the disulfide and cysteine interactions.
The main story of vitamin K epoxide reductase can be shown through the steps of the catalytic cycle shown on this slide. The first step of the catalytic cycle I want to highlight is the top right confirmation in which KOH is bound  in the active site of VKOR. Later Emma will go into some details about the bonds that occur within VKOR that stabilize this bond, but right now the most important thing to know is that KOH exists within the closed conformation of VKOR. In the second stage the conformation of VKOR changes, the amino acid residues behave differently, but the KH substrate still exists within the closed conformation. The third step to highlight is the open conformation of VKOR. On this diagram it is shown in many different ways, first with each of our previously mentioned substrates and finally with warfarin bound (which is called a closed conformation). This is labeled a closed conformation not because the actual cap is bound to the helices like in previous steps but because warfarin is a vitamin K antagonist and prevents KOH from binding the active site of our protein. Finally VKOR can also exist in the closed conformation with warfarin because as Emma mentioned there are a lot of similarities in the interactions between KOH and warfarin with vitamin k epoxide reductase.  


===Catalytic Cysteines===
===Catalytic Cysteines===
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