User:Tori Templin/Sandbox 1: Difference between revisions
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[[Image:Screen Shot 2021-03-16 at 3.11.39 PM.png|400 px|right|thumb|Figure 1. ACAT as a Dimer of Dimers - One Monomer is Highlighted]] | [[Image:Screen Shot 2021-03-16 at 3.11.39 PM.png|400 px|right|thumb|Figure 1. ACAT as a Dimer of Dimers - One Monomer is Highlighted]] | ||
[https://en.wikipedia.org/wiki/Sterol_O-acyltransferase ACAT] is an important enzyme that catalyzes the esterification of cholesterol to form cholesterol esters, and it belongs to the class of enzymes called acyltransferases. It is also a member of the [https://en.wikipedia.org/wiki/MBOAT MBOAT] family because it is key in lipid metabolism. This enzyme is biologically important because it affects the solubility of cholesterol in the cell membrane and promotes accumulation of cholesterol ester in the cytoplasm as fat droplets. Accumulation of cholesterol ester as these lipid droplets is a main characteristic of macrophage foaming, which can lead to atherosclerotic diseases <ref name=”Qian”>PMID:32433614</ref>. | [https://en.wikipedia.org/wiki/Sterol_O-acyltransferase ACAT] is an important enzyme that catalyzes the esterification of cholesterol to form cholesterol esters, and it belongs to the class of enzymes called acyltransferases. It is also a member of the [https://en.wikipedia.org/wiki/MBOAT MBOAT] family because it is key in lipid metabolism. This enzyme is biologically important because it affects the solubility of cholesterol in the cell membrane and promotes accumulation of cholesterol ester in the cytoplasm as fat droplets. Accumulation of cholesterol ester as these lipid droplets is a main characteristic of macrophage foaming, which can lead to atherosclerotic diseases <ref name=”Qian”>PMID:32433614</ref>. | ||
[[Image: | [[Image:Screen_Shot_2021-04-13_at_2.37.52_PM.jpg|400 px|right|thumb|Figure 2. Dimer in the Membrane]] | ||
SOAT article <ref name=”Chengcheng”>PMID:32424158</ref> | SOAT article <ref name=”Chengcheng”>PMID:32424158</ref> | ||
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This | This | ||
<scene name='87/877604/Tetramer/2'>tetramer</scene> | <scene name='87/877604/Tetramer/2'>tetramer</scene> | ||
is about 260 kDa and is composed completely of helices, with each monomer containing 9 transmembrane helices, which have been color-coordinated to help with orientation within structures. | is about 260 kDa and is composed completely of helices, with each monomer containing 9 transmembrane helices, which have been color-coordinated to help with orientation within structures. [[Image:Screen_Shot_2021-04-13_at_3.17.02_PM.jpg|400 px|right|thumb|Figure 3. Monomer in the Membrane. This shows the 9 transmembrane helices. Each are labeled and colored according to the active dimer.]] | ||
The | The | ||
<scene name='87/877604/Colored_dimer/3'>dimer of ACAT</scene> | <scene name='87/877604/Colored_dimer/3'>dimer of ACAT</scene> | ||
was found to be the active arrangement. | was found to be the active arrangement. | ||
The | The | ||
<scene name='87/877604/Dimer_interface/ | <scene name='87/877604/Dimer_interface/16'>dimer-dimer interface</scene> | ||
is mobile and mostly hydrophobic, and the residues interact in a shape-complementary manner. It was also found that the reaction chamber is shielded by a lid from the cytosolic side, which leads to low catalytic activity. The binding of acyl-CoA and cholesterol induce conformational changes that activate the tunnels. Work is still being done to fully determine the mechanism of this reaction, but this is the proposed pathway. The cholesterol enters through the T tunnel while the acyl-CoA enters through the C tunnel. The reaction is catalyzed at the intersection of the two tunnels, where the His460 residue is located. The CoASH is released to the cytosol from the C tunnel, but the cholesterol ester either exits from the T tunnel to the membrane or through the L tunnel to the lumen. | is mobile and mostly hydrophobic, and the residues interact in a shape-complementary manner. It was also found that the reaction chamber is shielded by a lid from the cytosolic side, which leads to low catalytic activity. The binding of acyl-CoA and cholesterol induce conformational changes that activate the tunnels. Work is still being done to fully determine the mechanism of this reaction, but this is the proposed pathway. The cholesterol enters through the T tunnel while the acyl-CoA enters through the C tunnel. The reaction is catalyzed at the intersection of the two tunnels, where the His460 residue is located. The CoASH is released to the cytosol from the C tunnel, but the cholesterol ester either exits from the T tunnel to the membrane or through the L tunnel to the lumen. | ||
== Relevance == | == Relevance == | ||
talk about inhibitor CI-976 | talk about inhibitor CI-976 | ||
<scene name='87/877626/Overlay/ | <scene name='87/877626/Overlay/10'>overlay</scene> | ||
<scene name='87/877626/Overlay/8'>CI976 vs. Inhibitor</scene> | <scene name='87/877626/Overlay/8'>CI976 vs. Inhibitor</scene> | ||
[[Image: CI- | [[Image: CI-976_chemdraw.jpg|300 px|right|thumb|Figure 4. CI-976 Inhibitor]] | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||