Small-Molecule Inhibitors of the m7G-RNA Writer METTL1.
ACS Bio Med Chem Au
; 4(2): 100-110, 2024 Apr 17.
Article
em En
| MEDLINE
| ID: mdl-38645929
ABSTRACT
We discovered the first inhibitors of the m7G-RNA writer METTL1 by high-throughput docking and an enzymatic assay based on luminescence. Eleven compounds, which belong to three different chemotypes, show inhibitory activity in the range 40-300 µM. Two adenine derivatives identified by docking have very favorable ligand efficiency of 0.34 and 0.31 kcal/mol per non-hydrogen atom, respectively. Molecular dynamics simulations provide evidence that the inhibitors compete with the binding of the cosubstrate S-adenosyl methionine to METTL1. We also present a soakable crystal form that was used to determine the structure of the complex of METTL1 with sinefungin at a resolution of 1.85 Å.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Bio Med Chem Au
Ano de publicação:
2024
Tipo de documento:
Article
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