6AIX

Crystal structure of DXO in complex with adenosine 3', 5' bisphosphate and two magnesium ions

6AIX の概要

• エントリーDOI: 10.2210/pdb6aix/pdb
• 分子名称: Decapping and exoribonuclease protein, ADENOSINE-3'-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: 5[prime]-3[prime] exoribonuclease, dxo, adenosine 3[ prime] and 5[prime] bisphosphate, nuclease inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43608.34

構造登録者

Chang, J.H.,Tong, L. (登録日: 2018-08-25, 公開日: 2018-10-17, 最終更新日: 2024-05-29)

主引用文献

Yun, J.S.,Yoon, J.H.,Choi, Y.J.,Son, Y.J.,Kim, S.,Tong, L.,Chang, J.H.
Molecular mechanism for the inhibition of DXO by adenosine 3',5'-bisphosphate.
Biochem. Biophys. Res. Commun., 504:89-95, 2018

PubMed 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-Mg complex at 1.8 Å resolution. In comparison with the DXO-RNA product complex, the position of pAp is well superimposed with the first nucleotide of the product RNA in the vicinity of two magnesium ions. Furthermore, biochemical assays showed that the inhibition by pAp is comparable between Xrn1 and DXO. Collectively, these structural and biochemical studies reveal that pAp inhibits the activities of DXO by occupying the active site to act as a competitive inhibitor.

PubMed: 30180947
DOI: 10.1016/j.bbrc.2018.08.135

実験手法

X-RAY DIFFRACTION (1.8 Å)