Interactions of the HIV-1 reverse transcriptase 'AZT-resistant' mutant with substrates and AZT-TP

FEBS Lett. 1993 Jul 5;325(3):237-41. doi: 10.1016/0014-5793(93)81080-j.

Abstract

To investigate the biochemical basis of the HIV-1 resistance to AZT we obtained the RT mutant containing four amino acid substitutions by an oligonucleotide-directed mutagenesis technique. Enzymatic properties of the wild type and mutant RTs were compared. 'AZT-resistant' mutations in RT were shown to be associated with the reduced capability of AZT-TP to block the DNA- but not RNA-directed DNA synthesis.

MeSH terms

  • Antiviral Agents / pharmacology*
  • DNA, Viral / biosynthesis
  • Dideoxynucleotides
  • Drug Resistance, Microbial / genetics
  • HIV Reverse Transcriptase
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • Mutagenesis, Site-Directed
  • RNA-Directed DNA Polymerase / genetics*
  • RNA-Directed DNA Polymerase / metabolism
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Inhibitors
  • Substrate Specificity
  • Thymine Nucleotides / pharmacology*
  • Zidovudine / analogs & derivatives*
  • Zidovudine / pharmacology

Substances

  • Antiviral Agents
  • DNA, Viral
  • Dideoxynucleotides
  • Recombinant Proteins
  • Reverse Transcriptase Inhibitors
  • Thymine Nucleotides
  • Zidovudine
  • zidovudine triphosphate
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase