Ann Taylor/HIV Protease
From Proteopedia
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HIV protease is categorized as an Aspartate Protease. This means that <scene name='User:David_Canner/Sandbox_HIV/Catalytic_asp/1'>aspartic acid side chains</scene> are required for its function. In HIV protease, one aspartic acid from each protein chain interacts with the <scene name='31/315240/Saquinavir_cat_water/2'>peptide chain</scene> to position it in a way that water can break the peptide bond. | HIV protease is categorized as an Aspartate Protease. This means that <scene name='User:David_Canner/Sandbox_HIV/Catalytic_asp/1'>aspartic acid side chains</scene> are required for its function. In HIV protease, one aspartic acid from each protein chain interacts with the <scene name='31/315240/Saquinavir_cat_water/2'>peptide chain</scene> to position it in a way that water can break the peptide bond. | ||
| - | ==How drugs inhibit HIV Protease== | ||
| - | <scene name='User:David_Canner/Sandbox_HIV/Saquinavir/4'>Saquinavir</scene> ([[Invirase]]) was the first protease inhibitor approved by the FDA for the treatment of HIV. It inhibits HIV protease by <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_tunnel/1'>binding tightly in the active site tunnel</scene>, preventing the binding of polyproteins. Its chemical structure mimics the tetrahedral intermediate of the hydrolytic reaction, thereby <scene name='User:David_Canner/Sandbox_HIV/Saquinavir_cat/3'>interacting strongly with the catalytic Asp residues</scene>.<ref>PMID:17243183</ref> Saquinavir is essentially an uncleavable ligand, as indicated by the <scene name='User:David_Canner/Sandbox_HIV/Hiv_morph2/9'> similar conformational changes in the protease flaps </scene> on binding saquinavir or a polypeptide. Resistance to saquinavir is due to alterations in the HIV protease sequence, including the mutation of <scene name='31/315240/Saquinavir_mut/1'>Leu 10 and Ile 50</scene><ref>PMID: 8969180</ref>. | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 16:41, 7 April 2022
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References
- ↑ Wlodawer A, Miller M, Jaskolski M, Sathyanarayana BK, Baldwin E, Weber IT, Selk LM, Clawson L, Schneider J, Kent SB. Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. Science. 1989 Aug 11;245(4918):616-21. PMID:2548279
- ↑ Lapatto R, Blundell T, Hemmings A, Overington J, Wilderspin A, Wood S, Merson JR, Whittle PJ, Danley DE, Geoghegan KF, et al.. X-ray analysis of HIV-1 proteinase at 2.7 A resolution confirms structural homology among retroviral enzymes. Nature. 1989 Nov 16;342(6247):299-302. PMID:2682266 doi:http://dx.doi.org/10.1038/342299a0
