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

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• 作者：Millie M Georgiadis ; Sven M Jessen ; Craig M Ogata ; Alice Telesnitsky ; Stephen P Goff ; Wayne A Hendrickson
• 关键词：HIV-1 ; metal ion site ; Moloney murine leukemia virus (MMLV) ; polymerase ; reverse transcriptase
• 刊名：Structure
• 出版年：1995
• 出版时间：September 1995
• 年：1995
• 卷：3
• 期：9
• 页码：879-892
• 全文大小：1995 K

文摘

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.