User:Kaitlyn Roberts/Sandbox 2
From Proteopedia
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It should be noted that this mechanism is largely hypothesized. Further analysis is needed to confirm the proposed steps. Additionally, the role of W420 is unclear. Mutations of W420A rendered the SOAT enzyme nonfunctional, indicating that it must be essential for catalytic activity. However, its role in the mechanism, direct or indirect, is unknown at this time. | It should be noted that this mechanism is largely hypothesized. Further analysis is needed to confirm the proposed steps. Additionally, the role of W420 is unclear. Mutations of W420A rendered the SOAT enzyme nonfunctional, indicating that it must be essential for catalytic activity. However, its role in the mechanism, direct or indirect, is unknown at this time. | ||
[[Image:SOATmech2.png|400 px|right|thumb|Figure 2. Mech 2]] | [[Image:SOATmech2.png|400 px|right|thumb|Figure 2. Mech 2]] | ||
+ | |||
+ | === Inhibitors === | ||
+ | CI-976 inhibits hSOAT activity in a dose-dependent manner. The location of CI-976 is found right in the <scene name='87/877559/Active_site_overview/1'>catalytic center</scene> with its large trimethoxyphenyl head sandwiched right between the catalytic residues <scene name='87/877559/Residues_and_inhibitor/17'>H460, W420, and N421</scene>. This suggests that CI-976 inhibits the enzyme by preventing the loading of the substrate into the catalytic center, which makes sense given the competitive behavior of CI-976. Mutations of CI-976 interaction residues, N421A, H460A, and H460N greatly diminish the enhancement effect of CI976 on the thermostability of the hSOAT dimer. | ||
== Biological Relevance == | == Biological Relevance == |
Revision as of 13:57, 6 April 2021
Human Sterol O-acyltransferase
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References
- ↑ 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
- ↑ 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
Student Contributors
- Kylie Pfifer
- Stepahnie Pellegrino
- Kaitlyn Roberts