Sandbox 645: Difference between revisions

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Ashraf Hasasneh, Tahreer Mutair, Charles Short

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 =='''Mechanism'''==
+Based on the hydrolysis mechanism. Water gets hydrolyzed by one of the aspartate residues , which leads to the formation of a tetrahedral oxyanion intermediate. This intermediate is formed by the water attack on the peptide carbonyl carbon.  Rearrangement leads to the protonation of the scissile amide and thus cleavage.
 [[Image:Mechanism aspartyl protease.png|500 px]]
 Mechanism for HIV-1 Protease
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 [[Image:Saquin1.gif|thumb|Saquinavir mesylate is a white to off-white, very fine powder with an aqueous solubility of 2.22 mg/mL at 25°C.]]
-)	Saquinavir (Invirase) is known to be one of the first FDA approved protease inhibitor for HIV treatment. This usually occurs by HIV protease binding an active site tunnel tightly, which will prevent polyproteins from also binding. HIV’s chemical structure has the ability to mimic the tetrahedral intermediate of the hydrolytic reaction to interact strong with the catalytic Asp residues.[[Image:Saquin1.gif|frame|Saquinavir mesylate is a white to off-white, very fine powder with an aqueous solubility of 2.22 mg/mL at 25°C.]] Knowing that, Saquinavir is an uncleavable ligand by studying its similar conformational changes in binding saquinavir or a polypeptide.   ((http://www.rxlist.com/invirase-drug.htm)))) Two types of mutants can result as a way of depleting the effectiveness of the saquinavir drug. These mutants are G48V and G48V/L90M. They cause 13.5 and 149 fold reductions, respectively. Based on some quantum mechanical and molecular mechanical analysis of the interaction of the saquinavir interaction; a disturbance of the saquinavir with the mutant with a flap residue 48 leads to a change in the hydrogen bonding. This mutation leads to the loss in the inhibitor/ enzyme binding.
+)	Saquinavir (Invirase) is known to be one of the first FDA approved protease inhibitor for HIV treatment. This usually occurs by HIV protease binding an active site tunnel tightly, which will prevent polyproteins from also binding. HIV’s chemical structure has the ability to mimic the tetrahedral intermediate of the hydrolytic reaction to interact strong with the catalytic Asp residues.[[Image:Saquin1.gif|frame|Saquinavir mesylate is a white to off-white, very fine powder with an aqueous solubility of 2.22 mg/mL at 25°C.]] Knowing that, Saquinavir is an uncleavable ligand by studying its similar conformational changes in binding saquinavir or a polypeptide. <ref>PMID: 20426757</ref> Two types of mutants can result as a way of depleting the effectiveness of the saquinavir drug. These mutants are G48V and G48V/L90M. They cause 13.5 and 149 fold reductions, respectively. Based on some quantum mechanical and molecular mechanical analysis of the interaction of the saquinavir interaction; a disturbance of the saquinavir with the mutant with a flap residue 48 leads to a change in the hydrogen bonding. This mutation leads to the loss in the inhibitor/ enzyme binding.