User:Emily Royston/Sandbox 2

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Desaturation of Fatty Stearoyl-CoA by SCD

1 Introduction
- 1.1 Overview
2 Structure
- 2.1 Binding Pocket
- 2.2 Metal Cations
3 Function
- 3.1 Desaturation Mechanism
- 3.2 Release of Product
4 Related Disease

Introduction

Overview

Stearoyl-CoA Desaturase (SCD) is an integral membrane protein located in the endoplasmic reticulum and is conserved across all eukaryotes (Bai et al., 2015). SCD-1 is expressed in Mus musculus. The human homolog, SCD1, shares 85% sequence identity with all four SCD’s found in M. musculus (Scd1-Scd4).

Stearoyl-CoA Desaturase is an enzyme which speeds up desaturation of a double bond within a fatty acid hydrocarbon chain. The addition of a double bond is necessary for the biosynthesis of monounsaturated fatty acids such as: cholesterol, phospholipids, and triglycerides. SCD-1 is able to interact with two different substrates: stearoyl-CoA or palmitoyl-CoA. Figure 1 represents the that stearoyl-CoA substrate fits in to interact with the enzyme. Within the enzyme there exists a di-iron complex that is stabilized by . SCD specifically catalyzes the C9-C10-cis desaturation of fatty stearoyl-CoA substrates from saturated fatty acids that come from an organism’s diet (Paton and Ntambi, 2009). Functioning SCD creates the balance between the accumulation and use of fats in the body. The enzyme plays a critical role in fatty acid metabolism pathways. Inhibition of SCD leads to possible treatment of metabolic disease and cancer.

Structure

Binding Pocket

Metal Cations

Function

Palmitoyl and Stearoyl CoA are substrates of SCD1. These substrates enter the hydrophobic V-shaped tunnel inside SCD1. The tunnel is regioselective and stereospecific such that the substrate’s binding site lines up C9 and C10 at the kink of the V-shaped tunnel with the di-iron center that consists of an oxygen molecule bound to one of the metals. The kink is formed by two conserved Trp149 and Thr257 residues. It is at this kink of the tunnel that desaturation occurs. Hydrogens are removed at the C9, then C10 to introduce the double bond through mechanism (link to mechanism section?). Precise placement of the C9-C10 atoms near the two iron metals provides the tunnel with regioselectivity and stereospecificity, stabilizing the substrate for oxygen to extract the hydrogens in order to form the double bond.

Desaturation Mechanism

Release of Product

Related Disease

References

Student Contributors

Brianna M. Avery
William J. Harris III
Emily M. Royston

Proteopedia Page Contributors and Editors (what is this?)

Emily Royston

Retrieved from "http://52.214.119.220/wiki/index.php/User:Emily_Royston/Sandbox_2"

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-=Stearoyl CoA Desaturase, SCD1 =
+=Desaturation of Fatty Stearoyl-CoA by SCD=
-<StructureSection load='4YMK' size='340' side='right' caption='Caption for this structure' scene=''>
-This is a default text for your page '''Emily Royston/Sandbox 2'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.
-You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
-== Introduction ==
+<StructureSection load='4YMK' size='350' frame='true' side='right' caption='Stearoyl-CoA Desaturase, SCD' scene='87/877504/Baseline_structure/2'>
-== Function ==
+==Introduction==
-== Disease ==
+===Overview===
+[https://en.wikipedia.org/wiki/Stearoyl-CoA_desaturase-1 Stearoyl-CoA Desaturase] (SCD) is an integral membrane protein located in the endoplasmic reticulum and is conserved across all eukaryotes (Bai et al., 2015). SCD-1 is expressed in Mus musculus. The human homolog, SCD1, shares 85% sequence identity with all four SCD’s found in M. musculus (Scd1-Scd4).
-== Structural highlights ==
+Stearoyl-CoA Desaturase is an enzyme which speeds up desaturation of a double bond within a fatty acid hydrocarbon chain. The addition of a double bond is necessary for the biosynthesis of monounsaturated fatty acids such as: cholesterol, phospholipids, and triglycerides. SCD-1 is able to interact with two different substrates: stearoyl-CoA or palmitoyl-CoA. Figure 1 represents the <scene name='87/877504/Baseline_structure/1'>depth of substrate tunnel</scene> that stearoyl-CoA substrate fits in to interact with the enzyme. Within the enzyme there exists a di-iron complex that is stabilized by <scene name='87/877517/Histidine1_emroy/4'>9 histidine residues</scene>. SCD specifically catalyzes the C9-C10-cis desaturation of fatty stearoyl-CoA substrates from saturated fatty acids that come from an organism’s diet (Paton and Ntambi, 2009). Functioning SCD creates the balance between the accumulation and use of fats in the body. The enzyme plays a critical role in fatty acid metabolism pathways. Inhibition of SCD leads to possible treatment of metabolic disease and cancer.
-=Student Contributers==
+==Structure==
+<scene name='87/877504/Tm_caption_1/1'>Mushroom-like Structure of SCD</scene>
-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.
+<scene name='87/877504/Trp_thr_creation_of_kink/1'>Creation of C9-C10 Double Bond</scene>
+===Binding Pocket===
+===Metal Cations===
+==Function==
+Palmitoyl and Stearoyl CoA are substrates of SCD1. These substrates enter the hydrophobic V-shaped tunnel inside SCD1. The tunnel is regioselective and stereospecific such that the substrate’s binding site lines up C9 and C10 at the kink of the V-shaped tunnel with the di-iron center that consists of an oxygen molecule bound to one of the metals. The kink is formed by two conserved Trp149 and Thr257 residues. It is at this kink of the tunnel that desaturation occurs. Hydrogens are removed at the C9, then C10 to introduce the double bond through mechanism (link to mechanism section?). Precise placement of the C9-C10 atoms near the two iron metals provides the tunnel with regioselectivity and stereospecificity, stabilizing the substrate for oxygen to extract the hydrogens in order to form the double bond.
+===Desaturation Mechanism===
+<scene name='87/877504/Zn_h_bond_stabilization_2/7'>C9-C10 Double Bond</scene>
+===Release of Product===
+==Related Disease==
 </StructureSection>
 == References ==
 <references/>
+==Student Contributors==
+*Brianna M. Avery
+*William J. Harris III
+*Emily M. Royston