PMID: 7535930Mar 28, 1995Paper

Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs

Proceedings of the National Academy of Sciences of the United States of America
Z GuM A Wainberg

Abstract

A lysine-to-arginine substitution at amino acid 65 (K65R) in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is associated with resistance to 2',3'-dideoxycytidine (ddC), 2',3'-dideoxyinosine (ddI), and the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC). To further characterize the molecular basis of such resistance, we expressed the pp6/p51 heterodimer of wild-type RT, K65R mutated RT, and a doubly mutated (K65R/M184V) RT in Escherichia coli and assessed the characteristics of nucleotide incorporation and chain termination in cell-free reverse transcription reactions in the presence and absence of various nucleoside triphosphate analogs. These reactions employed a HIV RNA template (HIV-PBS) that contained the primer binding sequence (PBS) and the U5 and R regions of HIV-1 genomic RNA and an oligodeoxynucleotide (dPR) complementary to the HIV-1 PBS as primer. The K65R and K65R/M184V RTs showed significantly decreased chain-termination effects during polymerization with the 5'-triphosphates of ddC, 3TC, 2',3'-dideoxyadenosine, and AZT (3'-azido-3'-deoxythymidine) in comparison with wild-type RT. Detailed analysis with ddCTP and wild-type RT revealed that chain termination occurred at all guanines in...Continue Reading

References

Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J L MartinP A Furman
Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·W Y GaoF Lori

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Citations

Jul 23, 2008·Biochemistry·Anthony J Berdis
May 5, 2000·The Biochemical Journal·N Sluis-CremerM A Parniak
Apr 5, 2002·Clinical Microbiology Reviews·Robert W Shafer
Apr 1, 2011·Future Microbiology·Shiro Ibe, Wataru Sugiura
Oct 8, 2009·Antiviral Research·Roger Paredes, Bonaventura Clotet
Nov 22, 2008·Journal of Molecular Biology·Stefan G SarafianosEddy Arnold
Nov 10, 2006·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·E J ArtsJ L Albright
Feb 12, 2008·Virus Research·Renato S Aguiar, B Matija Peterlin
Feb 8, 2008·Virus Research·Truus E M Abbink, Ben Berkhout
Sep 25, 2007·Antiviral Research·Claudio Cesar Cirne-SantosDumith Chequer Bou-Habib
Jan 20, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Max von Kleist, Wilhelm Huisinga
Jun 5, 2007·Antiviral Chemistry & Chemotherapy·Fernando A FrankelMark A Wainberg
Jul 1, 1995·Nature Medicine·M A Wainberg, Z Gu
Oct 16, 2004·Expert Review of Anti-infective Therapy·Matthias Götte
Aug 16, 1996·The Journal of Biological Chemistry·D ArionM A Parniak

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