Overview and Preliminary Questions
HIV reverse transcriptase is a key enzyme in the function of the immunodeficiency virus that causes AIDS (and all other retroviruses). Because the process of reverse transcription does not normally occur in human cells, this enzyme is unique to the virus and makes an excellent target for anti-HIV drug development.
1. What is transcription? What function does the enzyme transcriptase (you can tell by the -ase ending that it is an enzyme) perform?
- 2. So what might reverse transcriptase do?
- 3. In order for HIV to infect a human cell, it needs to incorporate its viral genetic information into the DNA of the human cell. But first, it needs to use its reverse transcriptase enzyme. What does this imply about the form of the nucleic acid that the genetic information is stored in HIV that it needs a reverse transcriptase?
- 4. What molecules would you therefore expect to find associated with this enzyme if the reverse transcriptase protein was crystallized “caught in the act”? If you get stuck here, move on the question 5.
The Structure
5. Looking at the model, can you identify the four subunits (two protein, one RNA and one DNA)? Referring back to your answer to question 4, which molecule is which? (Hint: If you are stuck, rotate the structure and look carefully at the shape of the 3rd subunit. Also, at this stage you will not be able to easily distinguish the DNA from RNA subunit).
- 6. Because viruses are not affected by antibiotics, researchers look for other drugs to stop viruses. Several of the promising anti-HIV drugs interact with HIV RT. Why do you think they target this protein? If you were designing one of these drugs, specifically what kind(s) of interaction(s) would you look for?
References
