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Functional Comparison of Reverse Transcriptase

Now that we have looked at the conformation and structure of HIV-1 reverse transcriptase, let us take a closer look at how HIV-1 RT specifically functions to polymerize a DNA strand. This tutorial is best viewed if the chime buttons are pressed in sequence.

This button will be the reset view for the unliganded reverse transcriptase.

This button will be the reset view for the reverse transcriptase with DNA.  

We have already looked at the unliganded reverse transcriptase complete with all it's functional subdomains and motifs. Let's now begin to look at a functional comparison of these featured subdomains and motifs in unliganded reverse transcriptase and reverse transcriptase polymerizing a DNA strand.

Let's first look at the two subdomains, p66 and p51. Notice that the location of the DNA and most of the enzymatic function occurs on the p66 subdomain.

As shown on the right, the thumb and fingers grip around the nucleic acid template (in this case, DNA) and hold it in place at the polymerase active site of the palm subdomain (Goldman & Marcey, 2001). The RNase H subdomain is shown, which usually cleaves an RNA template, but in this case a DNA template is being used to polymerize the complimentary strand, and hence RNase H is not needed. The trio of aspartic acid residues (110, 185, 186) at the polymerase active site interact with the 3' of the DNA primer and incorporate new nucleotides onto the DNA template (Doublie, Sawaya, & Ellenberger, 1999).

Because reverse transcriptase is a critical enzyme used by HIV-1, many scientists are trying to target this specific site (shown in both panels) to inhibit enzymatic function. Such inhibition could prevent HIV-1 from replicating within a cell. This now concludes the chime tutorial of the structural and functional features of HIV-1 reverse transcriptase.


Doublie S, Sawaya MR, Ellenberger T. 1999. An open and closed case for all polymerases. Structure (7)2. <http://www.sciencedirect
>. Accessed 2005 Feb 12.

Goldman M, Marcey D. 2001. HIV-1 Reverse Transcriptase. The Online Molecular Museum. <
>. Accessed 2005 Feb 12.

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