Sandbox Reserved 712
From Proteopedia
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HIV protease inhibitors are the most potent agens used in anti-HIV treatment. However it occurs that HIV-PR develop a resistance to the inhibitor. <ref> PMID:12543689 </ref> | HIV protease inhibitors are the most potent agens used in anti-HIV treatment. However it occurs that HIV-PR develop a resistance to the inhibitor. <ref> PMID:12543689 </ref> | ||
| - | 3ggu (also PRdrv5) is a mutated clinically derived PR that shows phenotypical resistance to darunavir. Darunavir is a human immunodeficiency virus (HIV) protease (PR) inhibitor (PI) which has inhibiting effects on many HIV type 1 PR variants that show resistance to earlier-generation-PIs. <ref> PMID:19535439 </ref> | + | 3ggu (also PRdrv5) is a mutated clinically derived PR that shows phenotypical resistance to darunavir. Darunavir is a human immunodeficiency virus (HIV) protease (PR) inhibitor (PI) which has inhibiting effects on many HIV type 1 PR variants that show resistance to earlier-generation-PIs. <ref name="Molecular"> PMID:19535439 </ref> |
== '''Activity''' == | == '''Activity''' == | ||
=== Prevalence of daruanvir resistance mutations in a large clinical database === | === Prevalence of daruanvir resistance mutations in a large clinical database === | ||
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=== Phenotypic susceptibiity to PIs === | === Phenotypic susceptibiity to PIs === | ||
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=== Enzymatic analysis of recombinant PRs === | === Enzymatic analysis of recombinant PRs === | ||
| - | Samples PRdrv1 to PRdrv6 have been cloned and expressed in ''E. coli''. Then they were purified anch characterized in vitro by monitoring cleavage of a chromogenic peptide substrate in the presence and absence of specific PIs. <ref | + | |
| + | Samples PRdrv1 to PRdrv6 have been cloned and expressed in ''E. coli''. Then they were purified anch characterized in vitro by monitoring cleavage of a chromogenic peptide substrate in the presence and absence of specific PIs. <ref name="Molecular" /> | ||
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=== X-ray strucure analysis of PRdrv1 and PRdrv5 === | === X-ray strucure analysis of PRdrv1 and PRdrv5 === | ||
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== '''Structure''' == | == '''Structure''' == | ||
Revision as of 14:59, 27 December 2012
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Contents |
Description
3ggu is a drug resistant HIV protease. Shown is a patient's variant in complex with darunavir.
HIV proteases (PR) are essential for the functioning of the retrovirus that causes AIDS. HIV needs active proteases to process gag & gap - polymerase polyprotein precursors into mature structural proteins and replicative enzymes. HIV proteases contain a highly conserved region Asp - Thr - Gly (Asp25, Thr26 and Gly27), with the aspartic residue beeing the active site in the aspartyl protease.[1]
Because of its importance for the life-cycle of the retrovirus, HIV-PR are the major target for anti-HIV treatment. HIV protease inhibitors are the most potent agens used in anti-HIV treatment. However it occurs that HIV-PR develop a resistance to the inhibitor. [2]
3ggu (also PRdrv5) is a mutated clinically derived PR that shows phenotypical resistance to darunavir. Darunavir is a human immunodeficiency virus (HIV) protease (PR) inhibitor (PI) which has inhibiting effects on many HIV type 1 PR variants that show resistance to earlier-generation-PIs. [3]
Activity
Prevalence of daruanvir resistance mutations in a large clinical database
Phenotypic susceptibiity to PIs
Enzymatic analysis of recombinant PRs
Samples PRdrv1 to PRdrv6 have been cloned and expressed in E. coli. Then they were purified anch characterized in vitro by monitoring cleavage of a chromogenic peptide substrate in the presence and absence of specific PIs. [3]
X-ray strucure analysis of PRdrv1 and PRdrv5
Structure
Applications
External Resources
References
- ↑ Kohl NE, Emini EA, Schleif WA, Davis LJ, Heimbach JC, Dixon RA, Scolnick EM, Sigal IS. Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4686-90. PMID:3290901
- ↑ Watkins T, Resch W, Irlbeck D, Swanstrom R. Selection of high-level resistance to human immunodeficiency virus type 1 protease inhibitors. Antimicrob Agents Chemother. 2003 Feb;47(2):759-69. PMID:12543689
- ↑ 3.0 3.1 Saskova KG, Kozisek M, Rezacova P, Brynda J, Yashina T, Kagan RM, Konvalinka J. Molecular characterization of clinical isolates of human immunodeficiency virus resistant to the protease inhibitor darunavir. J Virol. 2009 Sep;83(17):8810-8. Epub 2009 Jun 17. PMID:19535439 doi:10.1128/JVI.00451-09
Contributors
Julia Baaske, Angelika Wackerl
