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Crystal structures of the reverse transcriptase-associated ribonuclease H domain of xenotropic murine leukemia-virus related virus

  1. Author:
    Zhou, D. W.
    Chung, S. H.
    Miller, M.
    Le Grice, S. F. J.
    Wlodawer, A.

  2. Author Address

    [Zhou, Dongwen; Miller, Maria; Wlodawer, Alexander] NCI, Prot Struct Sect, MCL, Frederick, MD 21702 USA. [Chung, Suhman; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, Retroviral Replicat Lab, HIV Drug Resistance Program, Frederick, MD 21702 USA.;Wlodawer, A (reprint author), NCI, Prot Struct Sect, MCL, Bldg 536,Rm 5, Frederick, MD 21702 USA;wlodawer@nih.gov
    1. Year: 2012
    2. Date: Mar
  2. Journal: Journal of Structural Biology
    1. 177
    2. 3
    3. Pages: 638-645
  4. Type of Article: Article
  5. ISSN: 1047-8477
  1. Abstract:

    The ribonuclease H (RNase H) domain of retroviral reverse transcriptase (RT) plays a critical role in the life cycle by degrading the RNA strands of DNA/RNA hybrids. In addition, RNase H activity is required to precisely remove the RNA primers from nascent (-) and (+) strand DNA. We report here three crystal structures of the RNase H domain of xenotropic murine leukemia virus-related virus (XMRV) RI. namely (i) the previously identified construct from which helix C was deleted, (ii) the intact domain, and (iii) the intact domain complexed with an active site alpha-hydroxytropolone inhibitor. Enzymatic assays showed that the intact RNase H domain retained catalytic activity, whereas the variant lacking helix C was only marginally active, corroborating the importance of this helix for enzymatic activity. Modeling of the enzyme-substrate complex elucidated the essential role of helix C in binding a DNA/RNA hybrid and its likely mode of recognition. The crystal structure of the RNase H domain complexed with beta-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1016/j.jsb.2012.02.006
  3. View record in Web of Science®
  4. WOS: 000301894900006

Library Notes

  1. Fiscal Year: FY2011-2012

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