Sandbox Reserved 1709: Difference between revisions

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[[Image:Ss_of_catalytic_mech.png|350 px| right| thumb | Figure 3. Mechanism of VKOR.]]

The catalytic mechanism of VKOR is highly regulated and uses <scene name='90/904314/Stage_4_catalytic_cycle/30'>4 catalytic cysteine residues</scene> to activate Vitamin K necessary for blood coagulation. Figure 3 highlights these reactions that allow the substrate to be catalyzed to its active form through a series of 4 stages. The enzyme begins in <scene name='90/904314/Vkor_with_ko/1'>stage I</scene> in the open conformation with the cap domain open to allow substrate binding. Once a substrate binds, the cap domain transitions to the closed conformation, initiating <scene name='90/904314/Stage_2_catalytic_cycle/2'>stage II</scene>. For this to occur, the C51-C132 disulfide bridge is attacked by reactive C43 located within the cap domain. This reaction forms a new disulfide bridge between C43 and C51 that pulls the cap domain over the binding pocket with the substrate bound to stabilize the closed conformation of VKOR, such that VKOR is now in stage II. Free cysteines are now available that provide strong stabilization of the closed conformation through interactions with the cap domain and the bound substrate. This puts the enzyme in <scene name='90/904314/Stage_3_catalytic_cycle/8'>stage III</scene>, where a free C135 is purposed to interact with the substrate within the binding pocket to stabilize it during activation. The catalytic free C132 located between the cap domain and helical tunnel is very reactive and will attack this C135 to break that interaction with the substrate and release the activated Vitamin K product into the blood stream to promote coagulation. Two very stable disulfide bridges between C43-C41 and C132-C135 are now present and VKOR is unbound, so the enzyme is in its final, unreactive <scene name='90/904314/Stage_4_catalytic_cycle/21'>stage IV</scene>. VKOR must undergo conformational changes to return to Stage 1 and reactivate its catalytic cysteines so that another molecule of Vitamin K can bind and become activated.

The catalytic mechanism of VKOR is highly regulated and uses <scene name='90/904314/Stage_4_catalytic_cycle/30'>4 catalytic cysteine residues</scene> to activate Vitamin K necessary for blood coagulation. Figure 3 highlights these reactions that allow the substrate to be catalyzed to its active form through a series of 4 stages. The enzyme begins in <scene name='90/904314/Vkor_with_ko/1'>stage I</scene> in the open conformation with the cap domain open to allow substrate binding. Once a substrate binds, the cap domain transitions to the closed conformation, initiating <scene name='90/904314/Stage_2_catalytic_cycle/3'>stage II</scene>. For this to occur, the C51-C132 disulfide bridge is attacked by reactive C43 located within the cap domain. This reaction forms a new disulfide bridge between C43 and C51 that pulls the cap domain over the binding pocket with the substrate bound to stabilize the closed conformation of VKOR, such that VKOR is now in stage II. Free cysteines are now available that provide strong stabilization of the closed conformation through interactions with the cap domain and the bound substrate. This puts the enzyme in <scene name='90/904314/Stage_3_catalytic_cycle/8'>stage III</scene>, where a free C135 is purposed to interact with the substrate within the binding pocket to stabilize it during activation. The catalytic free C132 located between the cap domain and helical tunnel is very reactive and will attack this C135 to break that interaction with the substrate and release the activated Vitamin K product into the blood stream to promote coagulation. Two very stable disulfide bridges between C43-C41 and C132-C135 are now present and VKOR is unbound, so the enzyme is in its final, unreactive <scene name='90/904314/Stage_4_catalytic_cycle/21'>stage IV</scene>. VKOR must undergo conformational changes to return to Stage 1 and reactivate its catalytic cysteines so that another molecule of Vitamin K can bind and become activated.

== Disease and Treatment ==

Sandbox Reserved 1709: Difference between revisions

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@@ Line 29: / Line 29: @@
 [[Image:Ss_of_catalytic_mech.png|350 px| right| thumb | Figure 3. Mechanism of VKOR.]]
-The catalytic mechanism of VKOR is highly regulated and uses <scene name='90/904314/Stage_4_catalytic_cycle/30'>4 catalytic cysteine residues</scene> to activate Vitamin K necessary for blood coagulation. Figure 3 highlights these reactions that allow the substrate to be catalyzed to its active form through a series of 4 stages. The enzyme begins in <scene name='90/904314/Vkor_with_ko/1'>stage I</scene> in the open conformation with the cap domain open to allow substrate binding. Once a substrate binds, the cap domain transitions to the closed conformation, initiating <scene name='90/904314/Stage_2_catalytic_cycle/2'>stage II</scene>. For this to occur, the C51-C132 disulfide bridge is attacked by reactive C43 located within the cap domain. This reaction forms a new disulfide bridge between C43 and C51 that pulls the cap domain over the binding pocket with the substrate bound to stabilize the closed conformation of VKOR, such that VKOR is now in stage II. Free cysteines are now available that provide strong stabilization of the closed conformation through interactions with the cap domain and the bound substrate. This puts the enzyme in <scene name='90/904314/Stage_3_catalytic_cycle/8'>stage III</scene>, where a free C135 is purposed to interact with the substrate within the binding pocket to stabilize it during activation. The catalytic free C132 located between the cap domain and helical tunnel is very reactive and will attack this C135 to break that interaction with the substrate and release the activated Vitamin K product into the blood stream to promote coagulation. Two very stable disulfide bridges between C43-C41 and C132-C135 are now present and VKOR is unbound, so the enzyme is in its final, unreactive <scene name='90/904314/Stage_4_catalytic_cycle/21'>stage IV</scene>. VKOR must undergo conformational changes to return to Stage 1 and reactivate its catalytic cysteines so that another molecule of Vitamin K can bind and become activated.
+The catalytic mechanism of VKOR is highly regulated and uses <scene name='90/904314/Stage_4_catalytic_cycle/30'>4 catalytic cysteine residues</scene> to activate Vitamin K necessary for blood coagulation. Figure 3 highlights these reactions that allow the substrate to be catalyzed to its active form through a series of 4 stages. The enzyme begins in <scene name='90/904314/Vkor_with_ko/1'>stage I</scene> in the open conformation with the cap domain open to allow substrate binding. Once a substrate binds, the cap domain transitions to the closed conformation, initiating <scene name='90/904314/Stage_2_catalytic_cycle/3'>stage II</scene>. For this to occur, the C51-C132 disulfide bridge is attacked by reactive C43 located within the cap domain. This reaction forms a new disulfide bridge between C43 and C51 that pulls the cap domain over the binding pocket with the substrate bound to stabilize the closed conformation of VKOR, such that VKOR is now in stage II. Free cysteines are now available that provide strong stabilization of the closed conformation through interactions with the cap domain and the bound substrate. This puts the enzyme in <scene name='90/904314/Stage_3_catalytic_cycle/8'>stage III</scene>, where a free C135 is purposed to interact with the substrate within the binding pocket to stabilize it during activation. The catalytic free C132 located between the cap domain and helical tunnel is very reactive and will attack this C135 to break that interaction with the substrate and release the activated Vitamin K product into the blood stream to promote coagulation. Two very stable disulfide bridges between C43-C41 and C132-C135 are now present and VKOR is unbound, so the enzyme is in its final, unreactive <scene name='90/904314/Stage_4_catalytic_cycle/21'>stage IV</scene>. VKOR must undergo conformational changes to return to Stage 1 and reactivate its catalytic cysteines so that another molecule of Vitamin K can bind and become activated.
 == Disease and Treatment ==