HIV-1 Reverse Transcriptase in Complex with Nevirapine: Difference between revisions
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== Nevirapine as an Anti-retroviral Drug == | == Nevirapine as an Anti-retroviral Drug == | ||
A wide variety of drugs have been developed to target this enzyme in order to decrease the infectivity of HIV and slow the progression of this chronic disease. One class of drugs, called non-nucleoside reverse transcriptase inhibitors (NNRTIs), contain compounds that bind noncompetitively to a hydrophobic pocket near the polymerase active site. Binding of these compounds inhibit polymerization of nucleic acid by distorting the protein. Nevirapine is a first generation NNRTI, which binds RT in a butterfly-like conformation. Several factors stabilize its interaction with RT's hydrophobic pocket, and the conformational changes it causes in RT essentially inhibits DNA synthesis. Unfortunately, single amino acid mutations in the binding pocket can significantly decrease the antiviral potency of this drug. | A wide variety of drugs have been developed to target this enzyme in order to decrease the infectivity of HIV and slow the progression of this chronic disease. One class of drugs, called non-nucleoside reverse transcriptase inhibitors (NNRTIs), contain compounds that bind noncompetitively to a hydrophobic pocket near the polymerase active site. Binding of these compounds inhibit polymerization of nucleic acid by distorting the protein. Nevirapine is a first generation NNRTI, which binds RT in a butterfly-like conformation. Several factors stabilize its interaction with RT's hydrophobic pocket, and the conformational changes it causes in RT essentially inhibits DNA synthesis. Unfortunately, single amino acid mutations in the binding pocket can significantly decrease the antiviral potency of this drug. | ||
== Structure of RT domains == | |||
The p66 and p55 domains are derived from cleavage of the same polyprotein precursor. They share a common amino terminus as a result and they combine to form an asymmetric heterodimer. The p66 subunit (color) contains the polymerase (color) and RNase H (color) domains. The p55 subunit (color) shares the same subdomains as p66 but in different positions resulting in different folding. The p55 subunit is therefore non-enzymatic, and instead stabilizes the proper folding of the catalytic p66 subunit. | |||
</StructureSection> | </StructureSection> | ||
