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A Chemical Probe for the Methyl Transferase PRMT5 with a Novel Binding Mode.
- Source :
-
ACS medicinal chemistry letters [ACS Med Chem Lett] 2020 Sep 28; Vol. 11 (11), pp. 2227-2231. Date of Electronic Publication: 2020 Sep 28 (Print Publication: 2020). - Publication Year :
- 2020
-
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.<br />Competing Interests: The authors declare no competing financial interest.
Details
- Language :
- English
- ISSN :
- 1948-5875
- Volume :
- 11
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- ACS medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 33214833
- Full Text :
- https://doi.org/10.1021/acsmedchemlett.0c00355