User:Megan Harris./Sandbox 1
From Proteopedia
(Difference between revisions)
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== Function == | == Function == | ||
| - | == Mechanism of Elbasvir == | + | == Structure and Mechanism of Elbasvir == |
| + | Elbasvir, MK-8742, is a tetra-cyclic indole based NS5A inhibitor that was experimentally obtained through the modification of MK-4882. Through efficacy studies of infected chimpanzees, Elbasvir was discovered as a diastereomer of the known compound, MK-4882 <ref>DOI: 10.1002/cmdc.201300343</ref>. Elbasvir has a structural formula of C49H55N9O7 and a molecular weight of 882.035 g/mol. It is a highly flexible protein with 13 rotatable bonds. It has four hydrogen bond donors and nine hydrogen bond acceptors <ref>National Center for Biotechnology Inforamtion. PubChem Compound Database; CID=71661251, https://pubchem.ncbi.nlm.nih.gov/compound/71661251#section=Chemical-and-Physical-Properties</ref>. | ||
Although the actual mechanism of Elbasvir as a NS5A inhibitor is unknown, several hypothetical mechanisms have been researched. The NS5A protein is a critical protein for both DNA replication and assembly in the hepatitis C virus. With critical roles in both processes, NS5A is an excellent source as a target for inhibitors. NS5A is naturally located in the endoplasmic reticulum of the cell. When inhibited, the protein is redistributed from the ER to lipid droplets. If the cellular location changed, NS5A would be unable to aid in viral replication, illustrating a form of protein inhibition that Elbasvir could cause. Another potential mechanism of NS5A inhibitors is the altering of the phosphorylation of the NS5A protein <ref>DOI: http://dx.doi.org/10.1016/j.jhep.2013.03.030</ref>. The function of the NS5A protein is highly dependent on the phosphorylation, both basal phosphorylation and hyperphosphorylation <ref>doi: 10.1128/JVI.00253-11</ref>. Since the phosphorylation of the NS5A protein is critical for protein function, altering the levels could impact the activity of the protein. | Although the actual mechanism of Elbasvir as a NS5A inhibitor is unknown, several hypothetical mechanisms have been researched. The NS5A protein is a critical protein for both DNA replication and assembly in the hepatitis C virus. With critical roles in both processes, NS5A is an excellent source as a target for inhibitors. NS5A is naturally located in the endoplasmic reticulum of the cell. When inhibited, the protein is redistributed from the ER to lipid droplets. If the cellular location changed, NS5A would be unable to aid in viral replication, illustrating a form of protein inhibition that Elbasvir could cause. Another potential mechanism of NS5A inhibitors is the altering of the phosphorylation of the NS5A protein <ref>DOI: http://dx.doi.org/10.1016/j.jhep.2013.03.030</ref>. The function of the NS5A protein is highly dependent on the phosphorylation, both basal phosphorylation and hyperphosphorylation <ref>doi: 10.1128/JVI.00253-11</ref>. Since the phosphorylation of the NS5A protein is critical for protein function, altering the levels could impact the activity of the protein. | ||
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== References == | == References == | ||
<references/> | <references/> | ||
| + | <ref>DOI: 10.1002/cmdc.201300343</ref> | ||
| + | <ref>National Center for Biotechnology Inforamtion. PubChem Compound Database; CID=71661251, https://pubchem.ncbi.nlm.nih.gov/compound/71661251#section=Chemical-and-Physical-Properties</ref> | ||
<ref>DOI: http://dx.doi.org/10.1016/j.jhep.2013.03.030</ref> | <ref>DOI: http://dx.doi.org/10.1016/j.jhep.2013.03.030</ref> | ||
<ref>doi: 10.1128/JVI.00253-11</ref> | <ref>doi: 10.1128/JVI.00253-11</ref> | ||
Revision as of 19:06, 13 November 2016
==Your Heading Here (maybe something like 'Structure')== 2
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References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
- ↑ Coburn CA, Meinke PT, Chang W, Fandozzi CM, Graham DJ, Hu B, Huang Q, Kargman S, Kozlowski J, Liu R, McCauley JA, Nomeir AA, Soll RM, Vacca JP, Wang D, Wu H, Zhong B, Olsen DB, Ludmerer SW. Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity. ChemMedChem. 2013 Dec;8(12):1930-40. doi: 10.1002/cmdc.201300343. Epub 2013 Oct, 14. PMID:24127258 doi:http://dx.doi.org/10.1002/cmdc.201300343
- ↑ National Center for Biotechnology Inforamtion. PubChem Compound Database; CID=71661251, https://pubchem.ncbi.nlm.nih.gov/compound/71661251#section=Chemical-and-Physical-Properties
- ↑ doi: https://dx.doi.org/http
- ↑ Fridell RA, Qiu D, Valera L, Wang C, Rose RE, Gao M. Distinct functions of NS5A in hepatitis C virus RNA replication uncovered by studies with the NS5A inhibitor BMS-790052. J Virol. 2011 Jul;85(14):7312-20. doi: 10.1128/JVI.00253-11. Epub 2011 May 18. PMID:21593143 doi:http://dx.doi.org/10.1128/JVI.00253-11
