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Antimicrobial Agents and Chemotherapy, May 2002, p. 1540-1545, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1540-1545.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effects of Specific Zidovudine Resistance Mutations and Substrate Structure on Nucleotide-Dependent Primer Unblocking by Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Peter R. Meyer,1 Suzanne E. Matsuura,1 Adviye A. Tolun,1 Ingrid Pfeifer,1 Antero G. So,2 John W. Mellors,3 and Walter A. Scott1*

Department of Biochemistry and Molecular Biology,1 Department of Medicine, University of Miami School of Medicine, Miami, Florida 33101,2 Graduate School of Public Health and School of Medicine, University of Pittsburgh and the Veterans Affairs Medical Center, Pittsburgh, Pennsylvania 152613

Received 6 September 2001/ Returned for modification 4 December 2001/ Accepted 4 February 2002

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.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, P.O. Box 016129, Miami, FL 33101-6129. Phone: (305) 243-6359. Fax: (305) 243-3342. E-mail: wscott{at}miami.edu.

Antimicrobial Agents and Chemotherapy, May 2002, p. 1540-1545, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1540-1545.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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