Download MendeleyStructure of HIV-1 Reverse Transcriptase with Pre-Translocation and Post-Translocation AZTMP-Terminated DNA
Sarafianos, S.G., Clark Jr., A.D., Das, K., Tuske, S., Birktoft, J.J., Ilankumaran, P., Ramesha, A.R., Sayer, J.M., Jerina, D.M., Boyer, P.L., Hughes, S.H., Arnold, E.(2002) EMBO J 21: 6614-6624
- PubMed: 12456667
- DOI: https://doi.org/10.1093/emboj/cdf637
- Primary Citation of Related Structures:
1N5Y, 1N6Q - PubMed 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.
Organizational Affiliation:
Center for Advanced Biotechnology and Medicine, 679 Hoes Lane, Piscataway, NJ 08854-5638, USA.
