Unknown

Dataset Information

0

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


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 ?-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 ?-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor.

SUBMITTER: Zhou D 

PROVIDER: S-EPMC3306455 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Zhou Dongwen D   Chung Suhman S   Miller Maria M   Grice Stuart F J Le SF   Wlodawer Alexander A  

Journal of structural biology 20120216 3


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 d  ...[more]

Similar Datasets

| S-EPMC3323693 | biostudies-literature
| S-EPMC3245923 | biostudies-literature
| S-EPMC3475449 | biostudies-literature
| S-EPMC3318313 | biostudies-literature
| S-EPMC2443788 | biostudies-literature
| S-EPMC4509971 | biostudies-literature
| S-EPMC5288710 | biostudies-literature
| S-EPMC3071813 | biostudies-literature
| S-EPMC3423011 | biostudies-literature
| S-EPMC3302341 | biostudies-literature