Sandbox Reserved 1709

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Revision as of 14:49, 22 March 2022

This is a default text for your page George G. Papadeas/Sandbox VKOR. Click above on edit this page to modify. Be careful with the < and > signs.

You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

1 Introduction
2 Structural Highlights
3 Function: Method of Coagulation
- 3.1 Brief Overview
- 3.2 Catalytic Mechanism
4 Disease and Treatment

Introduction

History of VKOR

Function and Biological Role

Author's Notes

Structural Highlights

Active Site

The plays a vital role in binding of any substrate or ligand to the VKOR. Upon binding, the VKOR will transition into a that will allow its catalytic mechanism to commence.

Cap Domain

Closed conformation

Anchor

Function: Method of Coagulation

Brief Overview

The will be prepped and waiting for a substrate or ligand to bind.

Catalytic Mechanism

The catalytic mechanism of VKOR is a critical part of its overall function in the body. Highly regulated enzymatic activity through the reactivity of catalytic cysteines allows VKOR to properly activate Vitamin K for its use in the body. The enzyme begins in , where it's in the open conformation with the cap domain open to allow in a substrate to bind to the active site. Once a substrate binds, the cap domain is initiated into the closed conformation. VKOR is now in . To further stabilize the closed conformation with the substrate bound, the cap domain helps initiate a catalytic reaction of cysteines to break the disulfide bridge that was stabilizing stage 1. 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 , where the catalytic free cysteines react to form a new disulfide bridge, releasing the activated substrate into the blood stream to promote anticoagulation. With two stable disulfide bridges and VKOR unbound, the enzyme is now in its final, unreactive . VKOR must undergo conformational changes to return to Stage 1 and restart the catalytic process to activate Vitamin K again.

Disease and Treatment

Afflictions

Inhibition

Mutations

Some key that can be detrimental to the VKOR structure are mutations of the . The two main residues, N80 and Y139, can be mutated to A80 and F139 creating a decrease in recognition and stabilization

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

References

↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644

Retrieved from "http://52.214.119.220/wiki/index.php/Sandbox_Reserved_1709"

@@ Line 11: / Line 11: @@
 == Structural Highlights==
 === Active Site ===
+The <scene name='90/906893/Active_site/2'>active site</scene> plays a vital role in binding of any substrate or ligand to the VKOR. Upon binding, the VKOR will transition into a <scene name='90/906893/Closed_conformation/4'>closed conformation</scene> that will allow its catalytic mechanism to commence.
 === Cap Domain ===
 <scene name='90/904314/Cap_Domain/1'>VKOR Cap Domain</scene>
@@ Line 21: / Line 23: @@
 == Function: Method of Coagulation ==
 === Brief Overview ===
+The <scene name='90/906893/Open_conformation/1'>open conformation</scene> will be prepped and waiting for a substrate or ligand to bind.
 === Catalytic Mechanism ===
-The catalytic mechanism of VKOR is a critical part of its overall function in the body. Highly regulated enzymatic activity through the reactivity of catalytic cysteines allows VKOR to properly activate Vitamin K for its use in the body. The enzyme begins in STAGE 1, where it's in the open conformation with the cap domain open to allow in a substrate to bind to the active site. Once a substrate binds, the cap domain is initiated into the closed conformation. VKOR is now in STAGE 2. To further stabilize the closed conformation with the substrate bound, the cap domain helps initiate a catalytic reaction of cysteines to break the disulfide bridge that was stabilizing stage 1. 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/1'>Stage 3</scene>, where the catalytic free cysteines react to form a new disulfide bridge, releasing the activated substrate into the blood stream to promote anticoagulation. With two stable disulfide bridges and VKOR unbound, the enzyme is now in its final, unreactive <scene name='90/904314/Stage_4_catalytic_cycle/1'>Stage 4</scene>. VKOR must undergo conformational changes to return to Stage 1 and restart the catalytic process to activate Vitamin K again.
+The catalytic mechanism of VKOR is a critical part of its overall function in the body. Highly regulated enzymatic activity through the reactivity of catalytic cysteines allows VKOR to properly activate Vitamin K for its use in the body. The enzyme begins in <scene name='90/906893/Stage_1_catalytic_cycle/1'>stage 1</scene>, where it's in the open conformation with the cap domain open to allow in a substrate to bind to the active site. Once a substrate binds, the cap domain is initiated into the closed conformation. VKOR is now in <scene name='90/906893/Stage_2_catalytic_cycle/1'>stage 2</scene>. To further stabilize the closed conformation with the substrate bound, the cap domain helps initiate a catalytic reaction of cysteines to break the disulfide bridge that was stabilizing stage 1. 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/1'>Stage 3</scene>, where the catalytic free cysteines react to form a new disulfide bridge, releasing the activated substrate into the blood stream to promote anticoagulation. With two stable disulfide bridges and VKOR unbound, the enzyme is now in its final, unreactive <scene name='90/904314/Stage_4_catalytic_cycle/1'>Stage 4</scene>. VKOR must undergo conformational changes to return to Stage 1 and restart the catalytic process to activate Vitamin K again.
 [[Image:VKOR_Stage_3_and_4_mechanism.png |400 px|right| thumb]]
 == Disease and Treatment ==
@@ Line 29: / Line 32: @@
 === Inhibition ===
 === Mutations ===
+Some key <scene name='90/906893/Active_site_mutations/1'>mutations</scene> that can be detrimental to the VKOR structure are mutations of the <scene name='90/906893/Active_site/2'>active site</scene>. The two main residues, N80 and Y139, can be mutated to A80 and F139 creating a decrease in recognition and stabilization
 This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.