3V1O

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

Summary for 3V1O

• Entry DOI: 10.2210/pdb3v1o/pdb
• Related: 3V1Q 3V1R
• Descriptor: Reverse transcriptase/ribonuclease H p80, SULFATE ION, (4R)-2-METHYLPENTANE-2,4-DIOL, ... (5 entities in total)
• Functional Keywords: reverse transcription, hydrolase
• Biological source: Xenotropic MuLV-related virus VP35 (XMRV)
• Cellular location: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor (Potential). Matrix protein p15: Virion (Potential). Capsid protein p30: Virion (Potential). Nucleocapsid protein p10: Virion (Potential): Q2F7J3
• Total number of polymer chains: 1
• Total formula weight: 20468.99

Authors

Zhou, D.,Wlodawer, A. (deposition date: 2011-12-09, release date: 2012-03-14, Last modification date: 2024-02-28)

Primary citation

Zhou, D.,Chung, S.,Miller, M.,Le Grice, S.F.,Wlodawer, A.
Crystal structures of the reverse transcriptase-associated ribonuclease H domain of xenotropic murine leukemia-virus related virus.
J.Struct.Biol., 177:638-645, 2012

PubMed 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) RT, 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 α-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 β-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor.

PubMed: 22366278
DOI: 10.1016/j.jsb.2012.02.006

Experimental method

X-RAY DIFFRACTION (1.876 Å)