The replication of the AIDS virus, HIV-1, requires three viral enzymes: reverse transcriptase (RT), protease, and integrase. Two of these, RT and protease, are the targets for the currently approved anti-HIV drugs. Unfortunately, prolonged anti-HIV therapy often leads to the development of resistant virus. We are trying to understand the structure and function(s) of both wild-type and drug-resistance HIV-1 RT, with the hope that this understanding will help in the development of more effective drugs and drug therapies. The figure above shows the three-dimensional structure of HIV-1 RT in complex with double-stranded DNA (the polymerase active site is shown in white at lower left; the RNase H active site, in white at upper right). In collaboration with the laboratory of Edward Arnold (Rutgers University), we have investigated the effects of mutations in the polymerase domain (including mutations that confer resistance to nucleoside-analog drugs) on both the structure and function of HIV-1 RT.

For more information about the HIV-1 RT structure, visit the following websites: HIV-1 RT, Arnold Laboratory, and Protein Data Bank.