6L94

The structure of the dioxygenase ABH1 from mouse

6L94 の概要

• エントリーDOI: 10.2210/pdb6l94/pdb
• 分子名称: Nucleic acid dioxygenase ALKBH1, FE (II) ION (3 entities in total)
• 機能のキーワード: dioxygenase, abh1, demethylation, rna binding protein, oxidoreductase
• 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: 45476.54

構造登録者

Xie, W.,Wang, C.,Li, H.,Zhang, Y. (登録日: 2019-11-08, 公開日: 2020-11-11, 最終更新日: 2023-11-22)

主引用文献

Li, H.,Zhang, Y.,Guo, Y.,Liu, R.,Yu, Q.,Gong, L.,Liu, Z.,Xie, W.,Wang, C.
ALKBH1 promotes lung cancer by regulating m6A RNA demethylation.
Biochem Pharmacol, 189:114284-114284, 2021

PubMed Abstract: Lung cancer has surpassed breast cancer as the leading cause of cancer death in females in developed countries and the leading cause of cancer death in males. Despite extensive research on lung cancer, the pathogenesis of lung cancer is not fully understood. ALKBH1 is a 2-oxoglutarate and Fe (II)-dependent dioxygenase responsible for the demethylation of 6-methyladenine (m6A) in RNA and is essential to multiple cellular processes in human. Numerous recent studies suggest that ALKBH1 plays a role in tumorigenesis and tumor progression, but the role of ALKBH1 in lung cancer is largely unknown. In this study, we demonstrated that the expression levels of ALKBH1 in lung cancer tissues and cells were up regulated. The invasion and migration abilities of lung cancer cells were significantly suppressed in vitro upon the silencing of ALKBH1 while they were significantly promoted upon its overexpression. We next characterized the enzyme biochemically by analyzing the contribution of essential residues Y184, H231, D233, H287, R338, and R344 to its m6A demethylation activity. Lastly, our 3.1-Å crystal structure of mouse ALKBH1 revealed that the N-terminal domain of the protein forms close contacted with the core catalytic domain and might be responsible for the recognition of nucleic acid substrates. In summary, our combined cellular, biochemical, and structural results provide insight into the potential ALKBH1-based drug design for cancer therapies.

PubMed: 33068553
DOI: 10.1016/j.bcp.2020.114284

実験手法

X-RAY DIFFRACTION (3.10012342058 Å)