Site-directed mutagenesis of HIV reverse transcriptase to probe enzyme processivity and drug binding

Curr Opin Biotechnol. 1994 Aug;5(4):414-21. doi: 10.1016/0958-1669(94)90051-5.


Site-directed mutagenesis has demonstrated that changes within the human immunodeficiency virus reverse transcriptase coding sequence alone can account for viral resistance to inhibitors. Inhibitor sensitivity of mutant enzymes in vitro correlates with the sensitivity of the virus to non-nucleoside inhibitors observed in vivo, but this is not the case with nucleoside analogs. Recent structural, kinetic, and site-directed mutagenesis studies demonstrate the importance of enzyme-nucleic acid contacts in determining enzyme sensitivity to inhibitors in vitro, as well as how accurately the reverse transcriptase synthesizes DNA.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / pharmacology*
  • Binding Sites / genetics
  • Drug Resistance, Microbial / genetics
  • HIV Reverse Transcriptase
  • HIV-1 / enzymology*
  • Mutagenesis, Site-Directed
  • RNA-Directed DNA Polymerase / genetics
  • RNA-Directed DNA Polymerase / metabolism*
  • Reverse Transcriptase Inhibitors*


  • Antiviral Agents
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase