HIV-1 Reverse Transcriptase in Complex with Nevirapine: Difference between revisions
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== Structure of RT domains == | == Structure of RT domains == | ||
[[image:RT Polymerase and RNase H domains.jpg|thumb|left|400px|'''RT Polymerase and RNase H domains. Reprinted from Esposito et al PMID:22778958''']] | |||
RT is an <scene name='HIV-1_Reverse_Transcriptase_in_Complex_with_Nevirapine/Nevirapine_ternary_complex/1'>asymmetric heterodimer</scene> composed of a 560 amino acid 66kDa subunit (p66) and a 440 amino acid 51kDa subunit (p51). The p66 and p55 domains are derived from cleavage of the same polyprotein precursor. The p51 is made from the C-terminal cleavage of the p66 subunit by HIV-1 protease. As a result, they share a common amino terminus, but the p51 subunit does not have an RNase H domain. | RT is an <scene name='HIV-1_Reverse_Transcriptase_in_Complex_with_Nevirapine/Nevirapine_ternary_complex/1'>asymmetric heterodimer</scene> composed of a 560 amino acid 66kDa subunit (p66) and a 440 amino acid 51kDa subunit (p51). The p66 and p55 domains are derived from cleavage of the same polyprotein precursor. The p51 is made from the C-terminal cleavage of the p66 subunit by HIV-1 protease. As a result, they share a common amino terminus, but the p51 subunit does not have an RNase H domain. | ||
The p66 subunit contains two enzymatically active domains, polymerase and RNase H. This polymerase is responsible for catalyzing the polymerization of DNA using either RNA or DNA as the template. There are three asp residues (D110, D185, D186) in polymerase's active site that play a key role in the enzyme's function and are referred to as the <scene name='HIV-1_Reverse_Transcriptase_in_Complex_with_Nevirapine/Pol_active_site_residues/2'>catalytic | The p66 subunit contains two enzymatically active domains, polymerase and RNase H. This polymerase is responsible for catalyzing the polymerization of DNA using either RNA or DNA as the template. There are three asp residues (D110, D185, D186) in polymerase's active site that play a key role in the enzyme's function and are referred to as the <scene name='HIV-1_Reverse_Transcriptase_in_Complex_with_Nevirapine/Pol_active_site_residues/2'>catalytic triad</scene>.<ref>PMID:22778958</ref> The endonucleolytic ribonuclease H (RNase H) specifically degrades the RNA strand of RNA:DNA duplexes that are produced during retrotranscription. RT has a right-hand structure.<ref>Steitz, Thomas A. DNA Polymerases: Structural Diversity and Common Mechanisms. Jour. Bio. Chem. 274:17395-17398 (1999). [http://www.jbc.org/content/274/25/17395.long DOI:10.1074/jbc.274.25.17395]</ref> The polymerase domain can be divided into several subdomains: the fingers (residues 1-85 and 118-155), palm (residues 86-117 and 156-236), thumb (237-318) and connecting (319-426). The RNase H domain consists of the C-terminal residues 427-560.<ref name="sluis">PMID:15544453</ref> | ||
The p51 subunit contains the same four subdomains as the polymerase domain in p66, but in different positions. The p51 subunit is therefore non-enzymatic, and instead stabilizes the proper folding of the catalytic p66 subunit. Instead of adopting an "open" catalytically-active conformation that can accommodate a nucleic acid template strand like p66, the p51 subunit is in a "closed" conformation and plays a largely structural role.<ref name="kohlstaedt">PMID:1377403</ref> | The p51 subunit contains the same four subdomains as the polymerase domain in p66, but in different positions. The p51 subunit is therefore non-enzymatic, and instead stabilizes the proper folding of the catalytic p66 subunit. Instead of adopting an "open" catalytically-active conformation that can accommodate a nucleic acid template strand like p66, the p51 subunit is in a "closed" conformation and plays a largely structural role.<ref name="kohlstaedt">PMID:1377403</ref> | ||
