3V1R: Crystal Structures Of The Reverse Transcriptase-Associated Ribonuclease H Domain Of Xmrv With Inhibitor Beta-Thujaplicinol

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 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.
PDB ID: 3V1RDownload
MMDB ID: 97988
PDB Deposition Date: 2011/12/9
Updated in MMDB: 2012/03
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 3V1R: monomeric; determined by author
Molecular Components in 3V1R
Label Count Molecule
Protein (1 molecule)
Reverse Transcriptase/ribonuclease H P80
Molecule annotation
Chemicals (8 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB