Analysis of amino insertion mutations in the fingers subdomain of HIV-1 reverse transcriptase

J Mol Biol. 1999 Mar 5;286(4):995-1008. doi: 10.1006/jmbi.1998.2508.

Abstract

In response to dideoxy inosine/hydroxyurea dual therapy, HIV-1 (human immunodeficiency virus type-1) variants were isolated that had a small amino acid insertion and flanking amino acid substitutions in the fingers subdomain of HIV-1. We have analyzed the reverse transcriptase variants for their effects on HIV-1 reverse transcriptase activity. The data suggests that the inserted amino acid residues are responsible for low-level resistance to the nucleoside analog ddITP, while the role of the flanking amino acid substitutions is to compensate for the deleterious effects of the insertion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Deoxyadenine Nucleotides / pharmacology
  • Didanosine / pharmacology
  • Dideoxynucleotides
  • Drug Resistance, Microbial / genetics
  • HIV Infections / virology
  • HIV Reverse Transcriptase / genetics*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • Humans
  • Kinetics
  • Mutagenesis, Insertional
  • Protein Conformation

Substances

  • Anti-HIV Agents
  • Deoxyadenine Nucleotides
  • Dideoxynucleotides
  • 2',3'-dideoxyadenosine triphosphate
  • HIV Reverse Transcriptase
  • Didanosine