AZT-resistant HIV-1 reverse transcriptase: Difference between revisions
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The nucleic-acid binding cleft is primarily formed by the p66 polymerase and RNase H subdomains. The p51 thumb and connection subdomains form the floor of the binding cleft. In this way, the binding cleft is positioned so that both the polymerase and the RNAse H active sites come in contact with the nucleic acid. | The nucleic-acid binding cleft is primarily formed by the p66 polymerase and RNase H subdomains. The p51 thumb and connection subdomains form the floor of the binding cleft. In this way, the binding cleft is positioned so that both the polymerase and the RNAse H active sites come in contact with the nucleic acid. | ||
When polymerase activity begins, [[reverse transcriptase]] binds to the nucleic acid substrate. | When polymerase activity begins, [[reverse transcriptase]] binds to the nucleic acid substrate. This results in a conformational change in the position of the p66 thumb from a closed conformation to an open conformation. The p66 fingers subdomain then undergoes a conformational change which allows it to close down on the incoming dNTP, helping it to align the 3'-OH of the primer, the alpha-phosphate of the dNTP, and the polymerase active site. This is the rate-limiting step in the polymerization reaction. Following the slow step, phosphodiester bonds are formed between the newly incorporated nucleoside and the primer with the existing pyrophosphate. Eventually the fingers undergo another conformational change so that they can open and release the pyrophosphate from the active site. | ||
The RNase H activity of [[reverse transcriptase]] is not currently well known. Because so much is known about the activity of polymerase, this is typically the target for [[reverse transcriptase]] inhibitors. | |||
==Inhibition of Reverse Transcriptase Activity== | ==Inhibition of Reverse Transcriptase Activity== | ||
