Sandbox Reserved 687
From Proteopedia
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<Structure load='1T03' size='500' frame='true' align='right' caption='HIV-1 reverse transcriptase crosslinked to tenofovir terminated template-primer' scene='Insert optional scene name here' /> | <Structure load='1T03' size='500' frame='true' align='right' caption='HIV-1 reverse transcriptase crosslinked to tenofovir terminated template-primer' scene='Insert optional scene name here' /> | ||
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Reverse Transcriptase: <scene name='Sandbox_Reserved_687/Rt_with_palm_structure_no_i/1'>p66 with DNA</scene> | Reverse Transcriptase: <scene name='Sandbox_Reserved_687/Rt_with_palm_structure_no_i/1'>p66 with DNA</scene> | ||
<scene name='Sandbox_Reserved_687/Rt_with_palm_structure_labels/2'>p66 and TFV</scene>Upon infection, [[HIV]] binds to the [[CD4]] receptor in a helper T cell or other CD4-presenting [[lymphocyte]]. The viral envelope is then fused with the cellular membrane allowing intracellular release of viral particles. The utilization of several enzymes helps to solidify the virus’s hold on the cell. HIV [[reverse transcriptase]] (RT) works to convert the viral single-stranded [[RNA]] (ssRNA) into [[DNA]]. HIV [[integrase]] then helps to incorporate the newly reverse transcribed DNA into the cellular genome. (Voet et al. 2008) | <scene name='Sandbox_Reserved_687/Rt_with_palm_structure_labels/2'>p66 and TFV</scene>Upon infection, [[HIV]] binds to the [[CD4]] receptor in a helper T cell or other CD4-presenting [[lymphocyte]]. The viral envelope is then fused with the cellular membrane allowing intracellular release of viral particles. The utilization of several enzymes helps to solidify the virus’s hold on the cell. HIV [[reverse transcriptase]] (RT) works to convert the viral single-stranded [[RNA]] (ssRNA) into [[DNA]]. HIV [[integrase]] then helps to incorporate the newly reverse transcribed DNA into the cellular genome. (Voet et al. 2008) | ||
| - | The structure of HIV-1 [[reverse transcriptase]] is a dimeric protein with a 66-kD polymerase (p66) domain and a 51-kD RNase H domain (p51). The enzyme has a hand-like conformation and possesses one active site and three catalytic functions: RNA-dependent DNA polymerization, RNA hydrolysis, and DNA replication. The p66 domain is an RNA-dependent DNA polymerase which binds viral RNA as well as DNA in its single palm-like active site. This diversity of function is brought about by the flexible nature of the hand-like p66 subunit. The p51 subunit is the RNase H domain which degrades the viral RNA after a daughter DNA strand has been synthesized. A structural overview helps us understand the basis of the high mutability of HIV. RNA, which forms the basis of the viral genetic material, is less stable than DNA and is more subject to modification or damage. In addition the reverse transcriptase polymerase domain lacks proofreading exonuclease activity. This lowers the fidelity of the reverse transcription. (Voet et al. 2008, Abbondanzieri et al. 2008) | + | The structure of HIV-1 [[reverse transcriptase]] is a dimeric protein with a 66-kD polymerase (p66) domain and a 51-kD RNase H domain (p51). The enzyme has a <scene name='Sandbox_Reserved_687/Hand-like_structure/1'>hand-like</scene> conformation and possesses one active site and three catalytic functions: RNA-dependent DNA polymerization, RNA hydrolysis, and DNA replication. The p66 domain is an RNA-dependent DNA polymerase which binds viral RNA as well as DNA in its single palm-like active site. This active site is lined with positive charges (blue) which interact with the negatively charged phosphodiester backbone of the <scene name='Sandbox_Reserved_687/Hand-like_structure_with_dna/1'>bound DNA/RNA</scene>. This diversity of function is brought about by the flexible nature of the hand-like p66 subunit. The p51 subunit is the RNase H domain which degrades the viral RNA after a daughter DNA strand has been synthesized. A structural overview helps us understand the basis of the high mutability of HIV. RNA, which forms the basis of the viral genetic material, is less stable than DNA and is more subject to modification or damage. In addition the reverse transcriptase polymerase domain lacks proofreading exonuclease activity. This lowers the fidelity of the reverse transcription. (Voet et al. 2008, Abbondanzieri et al. 2008) |
==[[Tenofovir]] (TFV)== | ==[[Tenofovir]] (TFV)== | ||
Revision as of 21:29, 2 May 2013
| This Sandbox is Reserved from 30/01/2013, through 30/12/2013 for use in the course "Biochemistry II" taught by Hannah Tims at the Messiah College. This reservation includes Sandbox Reserved 686 through Sandbox Reserved 700. |
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Contents |
Complera: Emtricitabine/rilpivirine/tenofovir
- Marketed by: Gilead Sciences and Janssen Therapeutics
- Major Indication: HIV infection
- Drug Class: Combination of nucleoside/tide reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor
- Date of FDA Approval: August 2011
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Reverse Transcriptase: Upon infection, HIV binds to the CD4 receptor in a helper T cell or other CD4-presenting lymphocyte. The viral envelope is then fused with the cellular membrane allowing intracellular release of viral particles. The utilization of several enzymes helps to solidify the virus’s hold on the cell. HIV reverse transcriptase (RT) works to convert the viral single-stranded RNA (ssRNA) into DNA. HIV integrase then helps to incorporate the newly reverse transcribed DNA into the cellular genome. (Voet et al. 2008)
The structure of HIV-1 reverse transcriptase is a dimeric protein with a 66-kD polymerase (p66) domain and a 51-kD RNase H domain (p51). The enzyme has a conformation and possesses one active site and three catalytic functions: RNA-dependent DNA polymerization, RNA hydrolysis, and DNA replication. The p66 domain is an RNA-dependent DNA polymerase which binds viral RNA as well as DNA in its single palm-like active site. This active site is lined with positive charges (blue) which interact with the negatively charged phosphodiester backbone of the . This diversity of function is brought about by the flexible nature of the hand-like p66 subunit. The p51 subunit is the RNase H domain which degrades the viral RNA after a daughter DNA strand has been synthesized. A structural overview helps us understand the basis of the high mutability of HIV. RNA, which forms the basis of the viral genetic material, is less stable than DNA and is more subject to modification or damage. In addition the reverse transcriptase polymerase domain lacks proofreading exonuclease activity. This lowers the fidelity of the reverse transcription. (Voet et al. 2008, Abbondanzieri et al. 2008)
Tenofovir (TFV)
Rilpivirine (RPV)
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RPV in the In red are the binding pocket residues p66 (Leu-100, Lys-101, Lys-103, Val-106, Thr-107, Val-108, Val-179, Tyr-181, Tyr-188, Val-189, Gly-190, Phe-227, Trp-229, Leu- 234, and Tyr-318) and p51(Glu-138). Singh et al.
Emtricitabine (ECT)
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