dNTP versus NTP discrimination by phenylalanine 451 in duck hepatitis B virus P protein indicates a common structure of the dNTP-binding pocket with other reverse transcriptases

Nucleic Acids Research
Jürgen BeckMichael Nassal

Abstract

Hepatitis B viruses, or hepadnaviruses, are small DNA-containing viruses that replicate through reverse transcription. Their prototype, HBV, causes severe liver disease in humans. The hepadnaviral P protein is an unusual reverse transcriptase (RT) that initiates DNA synthesis by host-factor-dependent protein priming on a specific RNA stem-loop template, epsilon, yielding a short DNA oligonucleotide covalently attached to the RT. This priming reaction can be reconstituted with in vitro-translated duck hepatitis B virus (DHBV) P protein. No direct structural data are available for any P protein. However, P proteins share a number of conserved motifs with other polymerases. Box A contains an invariant bulky residue recently shown to be crucial for dNTP versus NTP discrimination in RTs and some DNA polymerases; its equivalent in DHBV P protein would be phenylalanine 451 (F451). Four mutants, containing glycine (F451G), alanine (F451A), valine (F451V) and aspartate (F451D), were therefore analyzed for their ability to utilize dNTPs and NTPs in in vitro priming. Priming efficiencies with dNTPs decreased with decreasing side chain size but GTP utilization increased; the wild-type enzyme was inactive with GTP. In the context of complet...Continue Reading

References

Jan 1, 1994·Annual Review of Biochemistry·C M Joyce, T A Steitz
Feb 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·J Hu, C Seeger
May 1, 1996·Trends in Biochemical Sciences·R Sousa
Sep 1, 1996·Journal of Viral Hepatitis·M Nassal, H Schaller
Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·G GaoS P Goff
Mar 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·C M Joyce
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·B S Blumberg
Jan 24, 1998·Nature·T A Steitz
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·M AstatkeC M Joyce
Jun 3, 1999·Nucleic Acids Research·A F Gardner, W E Jack
Jun 11, 1999·The Journal of Biological Chemistry·T A Steitz
Sep 15, 1999·Proceedings of the National Academy of Sciences of the United States of America·U ProtzerH Schaller
Mar 8, 2000·Microbiology and Molecular Biology Reviews : MMBR·C Seeger, W S Mason
Jun 9, 2001·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·D Mutimer

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Citations

Jan 14, 2011·Biochemistry·Jessica A Brown, Zucai Suo
Nov 13, 2014·Critical Reviews in Biochemistry and Molecular Biology·Jeremy W SchroederLyle A Simmons
Mar 15, 2008·Virus Research·Michael Nassal
Apr 22, 2015·Future Virology·Daniel N Clark, Jianming Hu
Sep 24, 2019·Nucleic Acids Research·Mary K JohnsonDeepak T Nair

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