Overview of polymerization.  The polymerization reaction can be divided into discreet steps.  HIV-1 RT is physically flexible; in addition, RT must move relative to the nucleic acid template as polymerization progresses.  The available crystal structures provide useful insights into the relationship between the movements of RT and the discreet steps in the polymerization reaction.  The relationship of the structures to progress in the polymerization reaction is shown in the figure above.

The available anti-RT drugs inhibit the polymerase activity; therefore, an understanding of the mechanism of polymerization is important for the development of more effective inhibitors.  In addition, our current understanding of drug resistance rests on an understanding of the enzymatic properties of RT.  More information about NRTIs and NRTI resistance can be found at Nucleoside RT Inhibitors; information about NNRTIs and NNRTI resistance can be found at Nonnucleoside RT Inhibitors.