Mutational analysis of the fingers and palm subdomains of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase

Paul L. Boyer, Andrea L. Ferris, Pat Clark, Jeff Whitmer, Peter Frank, Chris Tantillo, Edward Arnold, Stephen H. Hughes

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

We have analyzed the human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) polymerase domain between amino acids 91 and 157 by site-directed mutagenesis. We have constructed a series of amino acid substitutions using BspMI cassettes, and have assayed the RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H activities of the mutant HIV-1 RTs. The regions of HIV-1 RT between amino acids 91 and 119 and between amino acids 151 and 157 lie within the palm subdomain and include part of the polymerase active site. A number of amino acids within these regions have been identified as being directly or indirectly involved with polymerization, since amino acid substitutions at these residues decrease the polymerase activity without affecting RNase H activity. The region of HIV-1 RT between amino acids 120 and 150 lies within the fingers subdomain of the HIV-1 polymerase. We believe that the fingers subdomain plays a role in positioning the template. Many aminoacid substitutions in this region decrease or abolish both the polymerase and the RNase H functions.

Original languageEnglish (US)
Pages (from-to)472-483
Number of pages12
JournalJournal of molecular biology
Volume243
Issue number3
DOIs
StatePublished - Oct 27 1994

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Keywords

  • HIV-1
  • Mutagenesis
  • Reverse transcriptase

Fingerprint Dive into the research topics of 'Mutational analysis of the fingers and palm subdomains of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase'. Together they form a unique fingerprint.

Cite this