7U30

PRMT5:MEP50 Complexed with Cyclonucleoside Compound 1

Summary for 7U30

• Entry DOI: 10.2210/pdb7u30/pdb
• Descriptor: Protein arginine N-methyltransferase 5, Methylosome protein 50, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: prmt5, inhibitor, cyclonucleoside, methyl transferase, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 109461.47

Authors

Palte, R.L. (deposition date: 2022-02-25, release date: 2022-06-01, Last modification date: 2024-10-30)

Primary citation

Kawamura, S.,Palte, R.L.,Kim, H.Y.,Sauri, J.,Sondey, C.,Mansueto, M.S.,Altman, M.D.,Machacek, M.R.
Design and synthesis of unprecedented 9- and 10-membered cyclonucleosides with PRMT5 inhibitory activity.
Bioorg.Med.Chem., 66:116820-116820, 2022

PubMed Abstract: Synthesis of medium-sized rings is known to be challenging due to high transannular strain especially for 9- and 10-membered rings. Herein we report design and synthesis of unprecedented 9- and 10-membered purine 8,5'-cyclonucleosides as the first cyclonucleoside PRMT5 inhibitors. The cocrystal structure of PRMT5:MEP50 in complex with the synthesized 9-membered cyclonucleoside 1 revealed its binding mode in the SAM binding pocket of PRMT5.

PubMed: 35594650
DOI: 10.1016/j.bmc.2022.116820

Experimental method

X-RAY DIFFRACTION (2.6 Å)