User:Kerry Frattarola/Sandbox 1: Difference between revisions

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== Mechanism ==

The active site of HIV-1 protease is inhibited by Indinavir 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. ~~(Don't know how to reference this)~~ Arg8 also plays a role in holding a substrate in place in the enzyme active site. When the Indinavir molecule enters the protease active site it imitates the transition state of Gag protein peptides. The virus' peptide bonds [-NH-CO-] can be cleaved via aspartic catalysis. Indinavir contains a hydroxyethylene [-CH2-CH(OH)-] site instead that cannot be cleaved by Asp25. The molecule becomes stuck inside the active site because of the hydrogen bonds between Arg8 and Indinavir's pyridine ring and the interactions between Gly27 and Indinavir's aromatic rings. This blocks all further cleavage of viral peptides by the protease molecule.

The active site of HIV-1 protease is inhibited by Indinavir 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 Indinavir molecule enters the protease active site it imitates the transition state of Gag protein peptides. The virus' peptide bonds [-NH-CO-] can be cleaved via aspartic catalysis. Indinavir 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 Indinavir's pyridine ring and the interactions between Gly27 and Indinavir's aromatic rings. This blocks all further cleavage of viral peptides by the protease molecule.

~~Indinavir acts with the Asp25, Thr26 and Gly27 subunits in the HIV-1 protease enzyme.<ref>PMID:11410934</ref>~~

== Cellular Effects ==

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 == Mechanism ==
-The active site of HIV-1 protease is inhibited by Indinavir 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. (Don't know how to reference this) Arg8 also plays a role in holding a substrate in place in the enzyme active site. When the Indinavir molecule enters the protease active site it imitates the transition state of Gag protein peptides. The virus' peptide bonds [-NH-CO-] can be cleaved via aspartic catalysis. Indinavir contains a hydroxyethylene [-CH2-CH(OH)-] site instead that cannot be cleaved by Asp25. The molecule becomes stuck inside the active site because of the hydrogen bonds between Arg8 and Indinavir's pyridine ring and the interactions between Gly27 and Indinavir's aromatic rings. This blocks all further cleavage of viral peptides by the protease molecule.
+The active site of HIV-1 protease is inhibited by Indinavir 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 Indinavir molecule enters the protease active site it imitates the transition state of Gag protein peptides. The virus' peptide bonds [-NH-CO-] can be cleaved via aspartic catalysis. Indinavir 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 Indinavir's pyridine ring and the interactions between Gly27 and Indinavir's aromatic rings. This blocks all further cleavage of viral peptides by the protease molecule.
-Indinavir acts with the Asp25, Thr26 and Gly27 subunits in the HIV-1 protease enzyme.<ref>PMID:11410934</ref>
 == Cellular Effects ==