User:Megan Fleshman/Sandbox1
From Proteopedia
(Difference between revisions)
Line 12: | Line 12: | ||
ACAT was experimentally determined as a [https://en.wikipedia.org/wiki/Tetramer tetramer], yet is functionally active as a dimer. | ACAT was experimentally determined as a [https://en.wikipedia.org/wiki/Tetramer tetramer], yet is functionally active as a dimer. | ||
This <scene name='87/877605/Tetramer/3'>tetramer</scene> is about 260 kDa and is composed of helices and loops, with each monomer containing 9 transmembrane helices (Figure 3). The <scene name='87/877604/Colored_dimer/4'>dimer of ACAT</scene> was found to be the active arrangement. | This <scene name='87/877605/Tetramer/3'>tetramer</scene> is about 260 kDa and is composed of helices and loops, with each monomer containing 9 transmembrane helices (Figure 3). The <scene name='87/877604/Colored_dimer/4'>dimer of ACAT</scene> was found to be the active arrangement. | ||
- | [[Image:Screen_Shot_2021-04-20_at_3.29.54_PM.jpg|400 px|left|thumb|Figure 2. | + | [[Image:Screen_Shot_2021-04-20_at_3.29.54_PM.jpg|400 px|left|thumb|Figure 2. The grey shaded region illustrates the lipid bilayer, oriented with the lumen side upward and cytosolic side on the bottom. The tunnels allowing access to the catalytic site are labeled]] |
The <scene name='87/877604/Dimer_interface/17'>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 <scene name='87/877604/Dimer_interface/17'>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. |
Revision as of 00:48, 26 April 2021
Acyl-Coenzyme Cholesterol Acetyltransferase (ACAT)
|
References
ACAT article [8] SOAT Article [9]
- ↑ Farese RV Jr. The nine lives of ACAT inhibitors. Arterioscler Thromb Vasc Biol. 2006 Aug;26(8):1684-6. doi:, 10.1161/01.ATV.0000227511.35456.90. PMID:16857957 doi:http://dx.doi.org/10.1161/01.ATV.0000227511.35456.90
- ↑ Qian H, Zhao X, Yan R, Yao X, Gao S, Sun X, Du X, Yang H, Wong CCL, Yan N. Structural basis for catalysis and substrate specificity of human ACAT1. Nature. 2020 May;581(7808):333-338. doi: 10.1038/s41586-020-2290-0. Epub 2020 May, 13. PMID:32433614 doi:http://dx.doi.org/10.1038/s41586-020-2290-0
- ↑ 3.0 3.1 3.2 3.3 3.4 Chang TY, Chang CC, Bryleva E, Rogers MA, Murphy SR. Neuronal cholesterol esterification by ACAT1 in Alzheimer's disease. IUBMB Life. 2010 Apr;62(4):261-7. doi: 10.1002/iub.305. PMID:20101629 doi:http://dx.doi.org/10.1002/iub.305
- ↑ 4.0 4.1 4.2 4.3 4.4 Shibuya Y, Chang CC, Chang TY. ACAT1/SOAT1 as a therapeutic target for Alzheimer's disease. Future Med Chem. 2015;7(18):2451-67. doi: 10.4155/fmc.15.161. Epub 2015 Dec 15. PMID:26669800 doi:http://dx.doi.org/10.4155/fmc.15.161
- ↑ Ayyagari VN, Wang X, Diaz-Sylvester PL, Groesch K, Brard L. Assessment of acyl-CoA cholesterol acyltransferase (ACAT-1) role in ovarian cancer progression-An in vitro study. PLoS One. 2020 Jan 24;15(1):e0228024. doi: 10.1371/journal.pone.0228024., eCollection 2020. PMID:31978092 doi:http://dx.doi.org/10.1371/journal.pone.0228024
- ↑ Vaziri ND, Liang KH. Acyl-coenzyme A:cholesterol acyltransferase inhibition ameliorates proteinuria, hyperlipidemia, lecithin-cholesterol acyltransferase, SRB-1, and low-denisty lipoprotein receptor deficiencies in nephrotic syndrome. Circulation. 2004 Jul 27;110(4):419-25. doi: 10.1161/01.CIR.0000136023.70841.0F. , Epub 2004 Jul 19. PMID:15262831 doi:http://dx.doi.org/10.1161/01.CIR.0000136023.70841.0F
- ↑ 7.0 7.1 Willner EL, Tow B, Buhman KK, Wilson M, Sanan DA, Rudel LL, Farese RV Jr. Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1262-7. doi: 10.1073/pnas.0336398100., Epub 2003 Jan 21. PMID:12538880 doi:http://dx.doi.org/10.1073/pnas.0336398100
- ↑ Qian H, Zhao X, Yan R, Yao X, Gao S, Sun X, Du X, Yang H, Wong CCL, Yan N. Structural basis for catalysis and substrate specificity of human ACAT1. Nature. 2020 May;581(7808):333-338. doi: 10.1038/s41586-020-2290-0. Epub 2020 May, 13. PMID:32433614 doi:http://dx.doi.org/10.1038/s41586-020-2290-0
- ↑ Guan C, Niu Y, Chen SC, Kang Y, Wu JX, Nishi K, Chang CCY, Chang TY, Luo T, Chen L. Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor. Nat Commun. 2020 May 18;11(1):2478. doi: 10.1038/s41467-020-16288-4. PMID:32424158 doi:http://dx.doi.org/10.1038/s41467-020-16288-4
Student Contributors
- Megan Fleshman, Tori Templin, Haylie Moehlenkamp