HIV-1 Integrase
HIV-1 integrase (IN) is encoded by HIV gag-pol gene and has recently gained interest as the newest target for anti-retroviral therapy. HAART has been used to treat HIV since the development of protease inhibitors in the mid- 1990s. Since then the mortality rate associated with HIV has dropped nearly four fold for those who use HAART. While the drug cocktail consisting of protease inhibitors (PI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and nucleoside reverse transcriptase inhibitors (NRTI) has clearly proven successful in delaying the onset of AIDS, numerous side effects have been associated with the long term use of anti-retrovirals. GI upset, peripheral glucose resistance, and lipodystrophy to name a few. For most such side effects are greatly outweighed by the success of HAART. However, for some such a regiman is intolerable and for others drug-resistant variants of the virus render some drugs nearly ineffective. The newest anti-retroviral is a HIV integrase inhibitor, the first on the market being raltegravir.
HIV IN is responsible for integrating retroviral DNA into the host cell's genome. While HIV IN has yet to be crystallized in complex with DNA, the prototype foamy virus integrase has been crystallized in complex with DNA and raltegravir. Such structural data should prove valuable in future drug design and discovering characteristics of such a class of enzymes.
The above rendering was taken using (PDB ID: 3L2T) thanks to beautiful work done by Stephen Hare et al (2010). Find out more information here
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