User:Megan Fleshman/Sandbox1
From Proteopedia
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==Mechanism== | ==Mechanism== | ||
| + | Tunnels | ||
| + | The catalytic site is accessed through three different tunnels that lead from the center catalytic domain of the monomer, to the lumen, cytosol, and transmembrane space. The tunnels allow the entrance of reactants into the acyl transferase mechanism and the exit of the products to the correct location depending on their function. | ||
| + | The C tunnel is open to the cytosolic side of the protein in which the Acyl CoA enters into the catalytic domain. | ||
| + | The T tunnel is the transmembrane tunnel in which the cholesterol enters into the catalytic domain space. Important residues of the T tunnel include Arginine262, Phenylalanine 263, and Leucine 306. These residues are important for the proper entrance and orientation of the cholesterol to allow for its deprotonation in the mechanism. | ||
| + | The L tunnel is used for the cholesterol ester product to be able to leave the lumen of the cell yet this exit mechanism is still unknown in addition to the cholesterol leaving to the transmembrane space through the T tunnel. | ||
The mechanism of the acyltransferase reaction occurs in the catalytic site one of the monomers in the dimer of ACAT1. The T tunnel and and C tunnel converge to the same space to allow the proper orientation of the Acyl CoA and the incoming cholesterol from the transmembrane. The Acyl CoA is oriented in a way to allow the His460 to act as a base catalyst to begin the reaction by deprotonation of the cholesterol which allows it to attack the carbonyl carbon which breaks the sulfur carbonyl bond (figure X). This mechanism produced Acyl-CoASH and cholesteryl ester. The Acyl-CcASH leaves through the C tunnel to the cytosol. | The mechanism of the acyltransferase reaction occurs in the catalytic site one of the monomers in the dimer of ACAT1. The T tunnel and and C tunnel converge to the same space to allow the proper orientation of the Acyl CoA and the incoming cholesterol from the transmembrane. The Acyl CoA is oriented in a way to allow the His460 to act as a base catalyst to begin the reaction by deprotonation of the cholesterol which allows it to attack the carbonyl carbon which breaks the sulfur carbonyl bond (figure X). This mechanism produced Acyl-CoASH and cholesteryl ester. The Acyl-CcASH leaves through the C tunnel to the cytosol. | ||
Revision as of 20:59, 5 April 2021
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References
- ↑ Ransey E, Paredes E, Dey SK, Das SR, Heroux A, Macbeth MR. Crystal structure of the Entamoeba histolytica RNA lariat debranching enzyme EhDbr1 reveals a catalytic Zn(2+) /Mn(2+) heterobinucleation. FEBS Lett. 2017 Jul;591(13):2003-2010. doi: 10.1002/1873-3468.12677. Epub 2017, Jun 14. PMID:28504306 doi:http://dx.doi.org/10.1002/1873-3468.12677
- ↑ 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
