HIV-1 Reverse Transcriptase (RT)

Reverse transcriptase (RT), an important enzyme in HIV-1, catalyzes the transcription of the viral single-stranded (ss) RNA into double-stranded (ds) DNA. HIV RT consists of two subunits, the larger p66 (Chain A in PDB) and the smaller p51 (Chain B in PDB) , with  the polymerase and ribonuclease H (Rnase H) catalytic sites being located on the former. The polymerase domain of HIV resembles the right hand with fingers, thumb, palm, and connection sub-domain. A crucial role of RT in life cycle of HIV-1 makes it the prime target of anti-retroviral therapy, such as non-nucleoside reverse transcriptase inhibitors (NNRTIs). The thumb and finger sub-domains of RT undergo conformational changes to perform the process of reverse transcription. The NNRTIs bind in the binding pocket is approximately 10 Å away from the polymerase in RT and disrupts the conformational flexibility of the enzyme

Figure: Different sub-domains of HIV RT, i.e. thumb (blue), finger (red), palm (violet), and connection sub-domain (green) along with bound NNRTI rilpivirine. Index for distance between finger and thumb, i.e. Trp 24 in the fingers and Lys 287 in the thumb are depicted with green spheres

Following are the different sub-domains in HIV-1 RT along with its residue range. 

Fingers (1–84)
Palm (85–119)
Fingers (120–150)
Palm (151–243)
Thumb (244–322)
Connection (323–437)
RNaseH (438–560)