Effects of specific zidovudine resistance mutations and substrate structure on nucleotide-dependent primer unblocking by human immunodeficiency virus type 1 reverse transcriptase.
Nucleotide-dependent unblocking of chain-terminated DNA by human immunodeficiency virus type 1 reverse transcriptase (RT) is enhanced by the presence of mutations associated with 3'-azido-3'-deoxythymidine (AZT) resistance. The increase in unblocking activity was greater for mutant combinations associated with higher levels of in vivo AZT resistance. The difference between mutant and wild-type activity was further enhanced by introduction of a methyl group into the nucleotide substrate and was decreased for a nonaromatic substrate, suggesting that pi-pi interactions between RT and an aromatic structure may be facilitated by these mutations.
Meyer
Peter R
PR
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, Florida 33101, USA.
Matsuura
Suzanne E
SE
Tolun
Adviye A
AA
Pfeifer
Ingrid
I
So
Antero G
AG
Mellors
John W
JW
Scott
Walter A
WA
D000998:Antiviral Agents / Q000494:pharmacology*; D017931:DNA Primers; D015226:Dinucleoside Phosphates / Q000737:chemistry / Q000378:metabolism; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D008958:Models, Molecular; D009154:Mutation; D009711:Nucleotides / Q000737:chemistry* / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013379:Substrate Specificity; D013698:Templates, Genetic; D015215:Zidovudine / Q000494:pharmacology*
D000998:Antiviral Agents; D017931:DNA Primers; D015226:Dinucleoside Phosphates; D009711:Nucleotides; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase