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.
Last
modified: 18 December 2008
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