6TTP

Crystal structure of the human METTL3-METTL14 complex bound to Compound 1/Adenosine (DHU_M3M_023)

6TTP の概要

• エントリーDOI: 10.2210/pdb6ttp/pdb
• 分子名称: N6-adenosine-methyltransferase catalytic subunit, N6-adenosine-methyltransferase non-catalytic subunit, ADENOSINE, ... (5 entities in total)
• 機能のキーワード: compound, complex, mettl3, mettl14, epitranscriptomic, 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: 117118.61

構造登録者

Bedi, R.K.,Huang, D.,Sledz, P.,Caflisch, A. (登録日: 2019-12-30, 公開日: 2020-03-04, 最終更新日: 2024-11-06)

主引用文献

Bedi, R.K.,Huang, D.,Eberle, S.A.,Wiedmer, L.,Sledz, P.,Caflisch, A.
Small-Molecule Inhibitors of METTL3, the Major Human Epitranscriptomic Writer.
Chemmedchem, 15:744-748, 2020

PubMed Abstract: The RNA methylase METTL3 catalyzes the transfer of a methyl group from the cofactor S-adenosyl-L-methionine (SAM) to the N atom of adenine. We have screened a library of 4000 analogues and derivatives of the adenosine moiety of SAM by high-throughput docking into METTL3. Two series of adenine derivatives were identified in silico, and the binding mode of six of the predicted inhibitors was validated by protein crystallography. Two compounds, one for each series, show good ligand efficiency. We propose a route for their further development into potent and selective inhibitors of METTL3.

PubMed: 32159918
DOI: 10.1002/cmdc.202000011

実験手法

X-RAY DIFFRACTION (2 Å)