AI Article Synopsis
- AZT resistance in HIV-1 involves the reverse transcriptase effectively excising AZTMP from the primer strand when certain conditions are met during the transcription process.
- Researchers determined the crystal structures of two complexes related to this process, providing insights into how AZTMP is excised and how translocation occurs in the enzyme.
- The findings indicate that structural differences between these complexes, particularly involving a specific loop (the YMDD loop), play a crucial role in moving the primer from one binding site to another after new nucleotides are added.
Article Abstract
AZT (3'-azido-3'-deoxythymidine) resistance involves the enhanced excision of AZTMP from the end of the primer strand by HIV-1 reverse transcriptase. This reaction can occur when an AZTMP-terminated primer is bound at the nucleotide-binding site (pre-translocation complex N) but not at the 'priming' site (post-translocation complex P). We determined the crystal structures of N and P complexes at 3.0 and 3.1 A resolution. These structures provide insight into the structural basis of AZTMP excision and the mechanism of translocation. Docking of a dNTP in the P complex structure suggests steric crowding in forming a stable ternary complex that should increase the relative amount of the N complex, which is the substrate for excision. Structural differences between complexes N and P suggest that the conserved YMDD loop is involved in translocation, acting as a springboard that helps to propel the primer terminus from the N to the P site after dNMP incorporation.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC136941 | PMC |
| http://dx.doi.org/10.1093/emboj/cdf637 | DOI Listing |
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