User:Kerry Frattarola/Sandbox 1: Difference between revisions

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== Mechanism ==

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~~[https://upload.wikimedia.org/wikipedia/commons/0/00/Aspartyl_protease_mechanism.png]~~. 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.

Revision as of 04:41, 6 December 2016 view source Kerry Frattarola (talk \| contribs) 71 edits No edit summary ← Older edit		Revision as of 04:43, 6 December 2016 view source Kerry Frattarola (talk \| contribs) 71 edits No edit summary Newer edit →
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	== Mechanism ==		== Mechanism ==
	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~~[https://upload.wikimedia.org/wikipedia/commons/0/00/Aspartyl_protease_mechanism.png]~~. 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.