Structures of HIV-1 reverse transcriptase with pre- and post-translocation AZTMP-terminated DNA
AUTOR(ES)
Sarafianos, Stefan G.
FONTE
Oxford University Press
RESUMO
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 Å 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=136941Documentos Relacionados
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