Molecular mechanism for the inhibition of DXO by adenosine 3',5'-bisphosphate.

ABSTRACT: The decapping exoribonuclease DXO functions in pre-mRNA capping quality control, and shows multiple biochemical activities such as decapping, deNADding, pyrophosphohydrolase, and 5'-3' exoribonuclease activities. Previous studies revealed the molecular mechanisms of DXO based on the structures in complexes with a product, substrate mimic, cap analogue, and 3'-NADP⁺. Despite several reports on the substrate-specific reaction mechanism, the inhibitory mechanism of DXO remains elusive. Here, we demonstrate that adenosine 3', 5'-bisphosphate (pAp), a known inhibitor of the 5'-3' exoribonuclease Xrn1, inhibits the nuclease activity of DXO based on the results of structural and biochemical experiments. We determined the crystal structure of the DXO-pAp-Mg²⁺ complex at 1.8 Å

SUBMITTER: Yun JS 

PROVIDER: S-EPMC6145842 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature