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 ~~viral~~ protein normally ~~would~~ 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 ~~specific~~ protein. ~~I wrote something but~~ can'~~t remember what it was~~.

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.

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

== Cellular Effects ==

Indinavir blocks the cleavage of ~~gag and gag-pol proteins~~. This inhibition does not allow for the maturation of new viral particles produced from infected cells. Viral particles that do not mature will not be able to infect new cells, lowering the viral load. Protease inhibitors do not have any effect on already infected cells but they do prevent further cell to cell transmission of the virus.

Indinavir blocks the cleavage of the Gag polyprotein. This inhibition does not allow for the maturation of new viral particles produced from infected cells. Viral particles that do not mature will not be able to infect new cells, lowering the viral load. Protease inhibitors do not have any effect on already infected cells but they do prevent further cell to cell transmission of the virus.

</StructureSection>

== References ==

@@ Line 10: / Line 10: @@
 == Mechanism ==
-The active site of HIV-1 protease is inhibited by Indinavir when the molecule interacts with the specific sites that a viral protein normally would 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 specific protein. I wrote something but can't remember what it was.
+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.
 Indinavir acts with the Asp25, Thr26 and Gly27 subunits in the HIV-1 protease enzyme.<ref>PMID:11410934</ref>
 == Cellular Effects ==
-Indinavir blocks the cleavage of gag and gag-pol proteins. This inhibition does not allow for the maturation of new viral particles produced from infected cells. Viral particles that do not mature will not be able to infect new cells, lowering the viral load. Protease inhibitors do not have any effect on already infected cells but they do prevent further cell to cell transmission of the virus.
+Indinavir blocks the cleavage of the Gag polyprotein. This inhibition does not allow for the maturation of new viral particles produced from infected cells. Viral particles that do not mature will not be able to infect new cells, lowering the viral load. Protease inhibitors do not have any effect on already infected cells but they do prevent further cell to cell transmission of the virus.
 </StructureSection>
 == References ==
 <references/>