Mechanistic implications from the structure of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase

Millie M. Georgiadis, Sven M. Jessen, Craig M. Ogata, Alice Telesnitsky, Stephen P. Goff, Wayne A. Hendrickson

Research output: Contribution to journalArticlepeer-review

144 Scopus citations


Background: Reverse transcriptase (RT) converts the single-stranded RNA genome of a retrovirus into a double-stranded DNA copy for integration into the host genome. This process requires ribonuclease H as well as RNA-  and DNA-directed DNA polymerase activities. Although the overall organization of HIV-1 RT is known from previously reported crystal structures, no structure of a complex including a metal ion, which is essential for its catalytic activity, has been reported. Results Here we describe the structures at 1.8 å resolution of a catalytically active fragment of RT from Moloney murine leukemia virus (MMLV) and at 2.6 å of a complex of this fragment with Mn2+ coordinated in the polymerase active site. On the basis of similarities with HIV-1 RT and rat DNA polymerase β, we have modeled template/primer and deoxyribonucleoside 5′-triphosphate substrates into the MMLV RT structure. Conclusion Our model, in the context of the disposition of evolutionarily conserved residues seen here at high resolution, provides new insights into the mechanisms of catalysis, fidelity, processivity and discrimination between deoxyribose and ribose nucleotides.

Original languageEnglish (US)
Pages (from-to)879-892
Number of pages14
Issue number9
StatePublished - Sep 1995


  • HIV-1
  • Moloney murine leukemia virus (MMLV)
  • metal ion site
  • polymerase
  • reverse transcriptase

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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