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

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

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

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
JournalStructure
Volume3
Issue number9
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

Moloney murine leukemia virus
RNA-Directed DNA Polymerase
DNA-Directed DNA Polymerase
Genome
RNA
Deoxyribonucleosides
Deoxyribose
Ribonuclease H
Ribose
Retroviridae
Catalysis
Catalytic Domain
Nucleotides
Metals
Ions
DNA
Human immunodeficiency virus 1 reverse transcriptase

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Mechanistic implications from the structure of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase. / Georgiadis, Millie; Jessen, Sven M.; Ogata, Craig M.; Telesnitsky, Alice; Goff, Stephen P.; Hendrickson, Wayne A.

In: Structure, Vol. 3, No. 9, 1995, p. 879-892.

Research output: Contribution to journalArticle

Georgiadis, Millie ; Jessen, Sven M. ; Ogata, Craig M. ; Telesnitsky, Alice ; Goff, Stephen P. ; Hendrickson, Wayne A. / Mechanistic implications from the structure of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase. In: Structure. 1995 ; Vol. 3, No. 9. pp. 879-892.
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