A Chemical Probe for the Methyl Transferase PRMT5 with a Novel Binding Mode.
ACS Med Chem Lett
; 11(11): 2227-2231, 2020 Nov 12.
Article
em En
| MEDLINE
| ID: mdl-33214833
ABSTRACT
Protein arginine methyltransferase 5 (PRMT5) is an enzyme that can symmetrically dimethylate arginine residues in histones and nonhistone proteins by using S-adenosyl methionine (SAM) as the methyl donating cofactor. We have designed a library of SAM analogues and discovered potent, cell-active, and selective spiro diamines as inhibitors of the enzymatic function of PRMT5. Crystallographic studies confirmed a very interesting binding mode, involving protein flexibility, where both the cofactor pocket and part of substrate binding site are occupied by these inhibitors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2020
Tipo de documento:
Article