Viruses 2009, 1(3), 657-677; doi:10.3390/v1030657
Review

Revisiting Plus-Strand DNA Synthesis in Retroviruses and Long Terminal Repeat Retrotransposons: Dynamics of Enzyme: Substrate Interactions

1 Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21228, USA 2 Center for Advanced Research in Biotechnology of the University of Maryland Biotechnology Institute and the National Institute of Standards and Technology, 9600 Gudelsky Drive, Rockville, MD 20850, USA 3 HIV Drug Resistance Program, NCI, National Institutes of Health, Frederick, MD 21702-1201, USA
* Author to whom correspondence should be addressed.
Received: 10 September 2009; in revised form: 28 October 2009 / Accepted: 4 November 2009 / Published: 4 November 2009
(This article belongs to the Special Issue Retroviral Enzymes)
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Abstract: Although polypurine tract (PPT)-primed initiation of plus-strand DNA synthesis in retroviruses and LTR-containing retrotransposons can be accurately duplicated, the molecular details underlying this concerted series of events remain largely unknown. Importantly, the PPT 3’ terminus must be accommodated by ribonuclease H (RNase H) and DNA polymerase catalytic centers situated at either terminus of the cognate reverse transcriptase (RT), and in the case of the HIV-1 enzyme, ~70Å apart. Communication between RT and the RNA/DNA hybrid therefore appears necessary to promote these events. The crystal structure of the HIV-1 RT/PPT complex, while informative, positions the RNase H active site several bases pairs from the PPT/U3 junction, and thus provides limited information on cleavage specificity. To fill the gap between biochemical and crystallographic approaches, we review a multidisciplinary approach combining chemical probing, mass spectrometry, NMR spectroscopy and single molecule spectroscopy. Our studies also indicate that nonnucleoside RT inhibitors affect enzyme orientation, suggesting initiation of plus-strand DNA synthesis as a potential therapeutic target.
Keywords: retroviruses; LTR-retrotransposons; polypurine tract; plus strand DNA synthesis; NMR spectroscopy; single molecule spectroscopy; antiviral strategies

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MDPI and ACS Style

Fabris, D.; Marino, J.P.; Le Grice, S.F.J. Revisiting Plus-Strand DNA Synthesis in Retroviruses and Long Terminal Repeat Retrotransposons: Dynamics of Enzyme: Substrate Interactions. Viruses 2009, 1, 657-677.

AMA Style

Fabris D, Marino JP, Le Grice SFJ. Revisiting Plus-Strand DNA Synthesis in Retroviruses and Long Terminal Repeat Retrotransposons: Dynamics of Enzyme: Substrate Interactions. Viruses. 2009; 1(3):657-677.

Chicago/Turabian Style

Fabris, Daniele; Marino, John P.; Le Grice, Stuart F. J. 2009. "Revisiting Plus-Strand DNA Synthesis in Retroviruses and Long Terminal Repeat Retrotransposons: Dynamics of Enzyme: Substrate Interactions." Viruses 1, no. 3: 657-677.

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