6OGN

Crystal structure of mouse protein arginine methyltransferase 7 in complex with SGC8158 chemical probe

「6NPG」から置き換えられました

6OGN の概要

• エントリーDOI: 10.2210/pdb6ogn/pdb
• 分子名称: Protein arginine N-methyltransferase 7, ZINC ION, 5'-S-(4-{[(4'-chloro[1,1'-biphenyl]-3-yl)methyl]amino}butyl)-5'-thioadenosine, ... (5 entities in total)
• 機能のキーワード: prmt7, sgc8158, chemical probe, structural genomics, structural genomics consortium, transferase
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 80952.60

構造登録者

Halabelian, L.,Dong, A.,Zeng, H.,Li, Y.,Hutchinson, A.,Seitova, A.,Bountra, C.,Edwards, A.M.,Arrowsmith, C.H.,Structural Genomics Consortium (SGC) (登録日: 2019-04-03, 公開日: 2019-04-17, 最終更新日: 2023-10-11)

主引用文献

Szewczyk, M.M.,Ishikawa, Y.,Organ, S.,Sakai, N.,Li, F.,Halabelian, L.,Ackloo, S.,Couzens, A.L.,Eram, M.,Dilworth, D.,Fukushi, H.,Harding, R.,Dela Sena, C.C.,Sugo, T.,Hayashi, K.,McLeod, D.,Zepeda, C.,Aman, A.,Sanchez-Osuna, M.,Bonneil, E.,Takagi, S.,Al-Awar, R.,Tyers, M.,Richard, S.,Takizawa, M.,Gingras, A.C.,Arrowsmith, C.H.,Vedadi, M.,Brown, P.J.,Nara, H.,Barsyte-Lovejoy, D.
Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.
Nat Commun, 11:2396-2396, 2020

PubMed Abstract: Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective, and cell-active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in cells is converted to SGC8158, a potent, SAM-competitive PRMT7 inhibitor. Inhibition or knockout of cellular PRMT7 results in drastically reduced levels of arginine monomethylated HSP70 family stress-associated proteins. Structural and biochemical analyses reveal that PRMT7-driven in vitro methylation of HSP70 at R469 requires an ATP-bound, open conformation of HSP70. In cells, SGC3027 inhibits methylation of both constitutive and inducible forms of HSP70, and leads to decreased tolerance for perturbations of proteostasis including heat shock and proteasome inhibitors. These results demonstrate a role for PRMT7 and arginine methylation in stress response.

PubMed: 32409666
DOI: 10.1038/s41467-020-16271-z

実験手法

X-RAY DIFFRACTION (2.4 Å)