HIV-1 reverse transcriptase (HIV-1 RT) (HIV-1 RT)

HIV-1 reverse transcriptase (RT) is a multifunctional enzyme essential for the replication of the human immunodeficiency virus, responsible for converting the viral single-stranded RNA genome into double-stranded DNA [1]. The enzyme operates as a p66/p51 heterodimer and possesses two primary catalytic activities: a DNA polymerase activity that can utilize both RNA and DNA templates, and an RNase H activity that degrades the RNA strand of RNA-DNA intermediates [2]. The DNA polymerase active site is the specific region where nucleotide incorporation occurs and is the primary target for two major classes of antiretroviral drugs: Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) [3]. NRTIs function as chain terminators by mimicking natural nucleotides but lacking the 3'-hydroxyl group necessary for further strand elongation [4]. In contrast, NNRTIs bind to an allosteric site near the polymerase active site, inducing a conformational change that inhibits the enzyme's catalytic efficiency [5]. Due to the lack of proofreading activity, the enzyme is prone to mutations that lead to drug resistance, making it a critical target for combination therapy and resistance monitoring [6].

Other names

RNA-directed DNA polymeraseRetroviral reverse transcriptasep66/p51 heterodimerHIV-1 RTReverse transcriptase

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) act as competitive inhibitors and chain terminators by mimicking natural deoxynucleotides; Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) act as allosteric inhibitors by binding to a hydrophobic pocket near the polymerase active site, inducing conformational changes that inhibit catalytic activity.