HIV-1 Reverse Transcriptase in Complex with Nevirapine: Difference between revisions
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== NNRTIs: Anti-retroviral Drugs == | == NNRTIs: Anti-retroviral Drugs == | ||
RT is a prime target for anti-HIV drugs because of its essential role in the viral life cycle. 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. Of the 26 anti-retroviral drugs approved by the FDA to treat individuals infected with HIV, 13 target the viral polymerase of RT.<ref>U.S.F.&D. Administration. http://www.fda.gov/ForConsumers/byAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm118915.htm</ref> 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. NNRTIs are a group of small hydrophobic compounds with diverse structures that allosterically inhibit HIV-1 but not HIV-2 RT.<ref>PMID: 1298242</ref> Recent pre-steady kinetics studies suggest that the conformational state and not the chemical step leading to nucleotide incorporation is blocked by a NNRTI, favoring the "primer grip distortion" model.<ref>PMID:9000632</ref> Binding of these compounds allosterically inhibit RT, causing its distortion and incompetent binding to dNTP. | RT is a prime target for anti-HIV drugs because of its essential role in the viral life cycle. 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. Of the 26 anti-retroviral drugs approved by the FDA to treat individuals infected with HIV, 13 target the viral polymerase of RT.<ref>U.S.F.&D. Administration. http://www.fda.gov/ForConsumers/byAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm118915.htm</ref> 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. NNRTIs are a group of small hydrophobic compounds with diverse structures that allosterically inhibit HIV-1 but not HIV-2 RT.<ref>PMID: 1298242</ref> Recent pre-steady kinetics studies suggest that the conformational state and not the chemical step leading to nucleotide incorporation is blocked by a NNRTI, favoring the "primer grip distortion" model.<ref>PMID:9000632</ref> Binding of these compounds allosterically inhibit RT, causing its distortion and incompetent binding to dNTP. | ||
[[image:Effect of NNRTI binding on DNA polymerization by RT.jpg|thumb|left|400px|'''Effect of NNRTI binding on DNA polymerization by RT. Reprinted by permission from Macmillan Publishers Ltd: Nature Structural & Molecular Biology, copyright 2012''']] | |||
== The NNRTI Binding Pocket == | == The NNRTI Binding Pocket == | ||
