Evaluation of Compounds Against Recombinant HIV Reverse Transcriptase.


Reverse transcriptase (RT) has attracted particular attention as a ...
Reverse transcriptase (RT) has attracted particular attention as a target enzyme for AIDS chemotherapy, because the enzyme catalyzes a crucial step in the HIV replicative cycle. Effective inhibition of this enzyme prevents the formation of proviral DNA. RT is endowed with three independent enzymatic activities (1,2). It has an RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP), and RNaseH activity. The first function catalyzes the polymerization of 2'-deoxynucleotides (2'-dNTPs) with viral genomic single-stranded RNA as template and an oligo DNA (or t-RNALys) as the primer. The second function of the enzyme hydrolyzes the RNA strand of the RNA-DNA hybrid (formed by the first function of the RT) to generate a single-stranded DNA chain. This will allow the third function of RT to happen, namely catalysis of the polymerization of 2'-dNTPs with single-stranded DNA as template and an oligo DNA as primer. The enzyme has, by that time, converted the viral single-stranded RNA genome to double-stranded DNA, which can now be circularized and incorporated into the host cell DNA by the virusencoded integrase.




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