6TTT

Crystal structure of the human METTL3-METTL14 complex bound to Compound 2 (ASI_M3M_140)

Summary for 6TTT

• Entry DOI: 10.2210/pdb6ttt/pdb
• Descriptor: N6-adenosine-methyltransferase catalytic subunit, N6-adenosine-methyltransferase non-catalytic subunit, (2~{S},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-~{N}-methyl-3,4-bis(oxidanyl)oxolane-2-carboxamide, ... (5 entities in total)
• Functional Keywords: compound, complex, mettl3, mettl14, epitranscriptomic, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 117145.64

Authors

Bedi, R.K.,Huang, D.,Sledz, P.,Caflisch, A. (deposition date: 2019-12-30, release date: 2020-03-04, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)