7ACD

Crystal structure of the human METTL3-METTL14 complex with compound T30 (UZH1a)

7ACD の概要

• エントリーDOI: 10.2210/pdb7acd/pdb
• 分子名称: N6-adenosine-methyltransferase catalytic subunit, N6-adenosine-methyltransferase non-catalytic subunit, 4-[(4,4-dimethylpiperidin-1-yl)methyl]-2-oxidanyl-~{N}-[[(3~{R})-3-oxidanyl-1-[6-[(phenylmethyl)amino]pyrimidin-4-yl]piperidin-3-yl]methyl]benzamide, ... (6 entities in total)
• 機能のキーワード: inhibitor, complex, mettl3, sinefungin, mettl14, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62407.39

構造登録者

Bedi, R.K.,Huang, D.,Caflisch, A. (登録日: 2020-09-10, 公開日: 2020-10-28, 最終更新日: 2024-11-13)

主引用文献

Moroz-Omori, E.V.,Huang, D.,Kumar Bedi, R.,Cheriyamkunnel, S.J.,Bochenkova, E.,Dolbois, A.,Rzeczkowski, M.D.,Li, Y.,Wiedmer, L.,Caflisch, A.
METTL3 Inhibitors for Epitranscriptomic Modulation of Cellular Processes.
Chemmedchem, 16:3035-3043, 2021

PubMed Abstract: The methylase METTL3 is the writer enzyme of the N -methyladenosine (m A) modification of RNA. Using a structure-based drug discovery approach, we identified a METTL3 inhibitor with potency in a biochemical assay of 280 nM, while its enantiomer is 100 times less active. We observed a dose-dependent reduction in the m A methylation level of mRNA in several cell lines treated with the inhibitor already after 16 h of treatment, which lasted for at least 6 days. Importantly, the prolonged incubation (up to 6 days) with the METTL3 inhibitor did not alter levels of other RNA modifications (i. e., m A, m A , m G), suggesting selectivity of the developed compound towards other RNA methyltransferases.

PubMed: 34237194
DOI: 10.1002/cmdc.202100291

実験手法

X-RAY DIFFRACTION (2.5 Å)