Structures of Reverse Transcriptase Pre- and Post-Excision Complexes Shed New Light on HIV-1 AZT Resistance
2011
Understanding HIV-1 Resistance to AZT
Commentary
Evidence: moderate
Author Information
Author(s): Scott Walter A.
Primary Institution: University of Miami Miller School of Medicine
Hypothesis
How do mutations in reverse transcriptase contribute to HIV-1 resistance to AZT?
Conclusion
The study reveals new structural insights into how HIV-1 reverse transcriptase mutations enhance resistance to AZT.
Supporting Evidence
- Mutant reverse transcriptase can efficiently excise AZT-monophosphate after incorporation.
- New binding sites for AMP in mutant enzymes were identified that do not exist in wild type.
- Enhanced excision activity is linked to specific mutations in the reverse transcriptase.
Takeaway
Scientists found that changes in a virus's enzyme help it resist a common medicine, making it harder to treat.
Methodology
The study used crystal structures of HIV-1 reverse transcriptase with and without AZT to analyze resistance mechanisms.
Digital Object Identifier (DOI)
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