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Antimicrob Agents Chemother. 2002 May;46(5):1540-5.

Effects of specific zidovudine resistance mutations and substrate structure on nucleotide-dependent primer unblocking by human immunodeficiency virus type 1 reverse transcriptase.

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Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, Florida 33101, USA.


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.

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