User:Kerry Frattarola/Sandbox 1: Difference between revisions

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~~<scene name='74/745991/Progress/2'>TextToBeDisplayed</scene>~~

==Human Immunodeficiency Virus protease inhibitor==

==Structure==

[[Crixivan]] is an antiviral compound that acts as a protease inhibitor~~. Figure 2 below depicts Crixivan’s structure~~. The drug has a molecular weight of 711.875 g/mol and is very soluble in water and ethanol <ref>Physicians Desk Reference 66th ed. PDR Network, LLC, Montvale, NJ. p. 2086 (2012)</ref>. Crixivan works by specifically binding to the HIV-1 protease active site by mimicking a target substrate protein and essentially becoming “stuck” in the enzyme active site, disabling the enzyme. ~~Crixivan’s~~ pyridine ~~attracts~~ protease ~~Arg8~~ to ~~hold it in place~~. ~~Its~~ ketone ~~interacts~~ with the protease ~~Asp25 to perform initiate aspartic catalysis. The~~ bond between the ketone and ~~amine~~ doesn't lyse due to the nature of the inhibitor.

[[Crixivan]] is an antiviral compound that acts as a protease inhibitor. The drug has a molecular weight of 711.875 g/mol and is very soluble in water and ethanol <ref>Physicians Desk Reference 66th ed. PDR Network, LLC, Montvale, NJ. p. 2086 (2012)</ref>. Crixivan works by specifically binding to the HIV-1 protease active site by mimicking a target substrate protein and essentially becoming “stuck” in the enzyme active site, disabling the enzyme. The pyridine group on Indinavir interacts with Arg8 in the protease to conform Indinavir to the active site. The ketone is attacked by with the Asp25 of the protease, forming a bond between the ketone and amide doesn't lyse due to the nature of the inhibitor.

== Function ==

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== Mechanism ==

The active site of HIV-1 protease is inhibited by Crixivan when the molecule interacts with the specific sites that a Gag protein peptide would normally interact with. The active site contains Asp25, which is involved in peptide cleavage, Thr26, which is involved in stabilizing the active site conformation, and Gly27, which is involved in the binding of a protein in a position that gives Asp25 access to its cleavage site. <ref>PMID:11410934</ref> Arg8 also plays a role in holding a substrate in place in the enzyme active site. When the Crixivan molecule enters the protease active site it imitates the transition state of Gag protein peptides during the cleavage reaction. The virus' peptide bonds [-NH-CO-] can be cleaved via aspartic catalysis. Crixivan contains a hydroxyethylene [-CH2-CH(OH)-] site instead that cannot be cleaved by Asp25.<ref>DOI:10.1002/rmv.624</ref> The molecule becomes stuck inside the active site because of the hydrogen bonds between Arg8 and Crixivan's pyridine ring and the interactions between Gly27 and Crixivan's aromatic rings. <ref>DOI:10.1111/j.1432-1033.2004.04060.x</ref> This blocks all further cleavage of viral peptides by the protease molecule.

The <scene name='74/745991/Progress/2'>active site</scene> of HIV-1 protease is inhibited by Crixivan when the molecule interacts with the specific sites that a Gag protein peptide would normally interact with. The active site contains Asp25, which is involved in peptide cleavage, Thr26, which is involved in stabilizing the active site conformation, and Gly27, which is involved in the binding of a protein in a position that gives Asp25 access to its cleavage site. <ref>PMID:11410934</ref> Arg8 also plays a role in holding a substrate in place in the enzyme active site. When the Crixivan molecule enters the protease active site it imitates the transition state of Gag protein peptides during the cleavage reaction. The virus' peptide bonds [-NH-CO-] can be cleaved via aspartic catalysis. Crixivan contains a hydroxyethylene [-CH2-CH(OH)-] site instead that cannot be cleaved by Asp25.<ref>DOI:10.1002/rmv.624</ref> The molecule becomes stuck inside the active site because of the hydrogen bonds between Arg8 and Crixivan's pyridine ring and the interactions between Gly27 and Crixivan's aromatic rings. <ref>DOI:10.1111/j.1432-1033.2004.04060.x</ref> This blocks all further cleavage of viral peptides by the protease molecule.

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-<scene name='74/745991/Progress/2'>TextToBeDisplayed</scene>
 ==Human Immunodeficiency Virus protease inhibitor==
 <StructureSection load='2b7z' size='340' side='right' caption='Structure of HIV-1 protease bound to indinavir, ([[2b7z]]), [[Resolution|resolution]] 2.20&Aring;' scene=''>
 ==Structure==
-[[Crixivan]] is an antiviral compound that acts as a protease inhibitor. Figure 2 below depicts Crixivan’s structure. The drug has a molecular weight of 711.875 g/mol and is very soluble in water and ethanol <ref>Physicians Desk Reference 66th ed. PDR Network, LLC, Montvale, NJ. p. 2086 (2012)</ref>. Crixivan works by specifically binding to the HIV-1 protease active site by mimicking a target substrate protein and essentially becoming “stuck” in the enzyme active site, disabling the enzyme. Crixivan’s pyridine attracts protease Arg8 to hold it in place. Its ketone interacts with the protease Asp25 to perform initiate aspartic catalysis. The bond between the ketone and amine doesn't lyse due to the nature of the inhibitor.
+[[Crixivan]] is an antiviral compound that acts as a protease inhibitor. The drug has a molecular weight of 711.875 g/mol and is very soluble in water and ethanol <ref>Physicians Desk Reference 66th ed. PDR Network, LLC, Montvale, NJ. p. 2086 (2012)</ref>. Crixivan works by specifically binding to the HIV-1 protease active site by mimicking a target substrate protein and essentially becoming “stuck” in the enzyme active site, disabling the enzyme. The pyridine group on Indinavir interacts with Arg8 in the protease to conform Indinavir to the active site. The ketone is attacked by with the Asp25 of the protease, forming a bond between the ketone and amide doesn't lyse due to the nature of the inhibitor.
 == Function ==
@@ Line 10: / Line 9: @@
 == Mechanism ==
-The active site of HIV-1 protease is inhibited by Crixivan when the molecule interacts with the specific sites that a Gag protein peptide would normally interact with. The active site contains Asp25, which is involved in peptide cleavage, Thr26, which is involved in stabilizing the active site conformation, and Gly27, which is involved in the binding of a protein in a position that gives Asp25 access to its cleavage site. <ref>PMID:11410934</ref>  Arg8 also plays a role in holding a substrate in place in the enzyme active site. When the Crixivan molecule enters the protease active site it imitates the transition state of Gag protein peptides during the cleavage reaction. The virus' peptide bonds [-NH-CO-] can be cleaved via aspartic catalysis. Crixivan contains a hydroxyethylene [-CH2-CH(OH)-] site instead that cannot be cleaved by Asp25.<ref>DOI:10.1002/rmv.624</ref> The molecule becomes stuck inside the active site because of the hydrogen bonds between Arg8 and Crixivan's pyridine ring and the interactions between Gly27 and Crixivan's aromatic rings. <ref>DOI:10.1111/j.1432-1033.2004.04060.x</ref> This blocks all further cleavage of viral peptides by the protease molecule.
+The <scene name='74/745991/Progress/2'>active site</scene> of HIV-1 protease is inhibited by Crixivan when the molecule interacts with the specific sites that a Gag protein peptide would normally interact with. The active site contains Asp25, which is involved in peptide cleavage, Thr26, which is involved in stabilizing the active site conformation, and Gly27, which is involved in the binding of a protein in a position that gives Asp25 access to its cleavage site. <ref>PMID:11410934</ref>  Arg8 also plays a role in holding a substrate in place in the enzyme active site. When the Crixivan molecule enters the protease active site it imitates the transition state of Gag protein peptides during the cleavage reaction. The virus' peptide bonds [-NH-CO-] can be cleaved via aspartic catalysis. Crixivan contains a hydroxyethylene [-CH2-CH(OH)-] site instead that cannot be cleaved by Asp25.<ref>DOI:10.1002/rmv.624</ref> The molecule becomes stuck inside the active site because of the hydrogen bonds between Arg8 and Crixivan's pyridine ring and the interactions between Gly27 and Crixivan's aromatic rings. <ref>DOI:10.1111/j.1432-1033.2004.04060.x</ref> This blocks all further cleavage of viral peptides by the protease molecule.