6DBP

RNA-recognition motif 1 of human MSI2

6DBP の概要

• エントリーDOI: 10.2210/pdb6dbp/pdb
• 分子名称: RNA-binding protein Musashi homolog 2 (2 entities in total)
• 機能のキーワード: musashi2 rna recognition motif, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19186.08

構造登録者

Goldgur, Y.,Kharas, M.G.,Minuesa, G. (登録日: 2018-05-03, 公開日: 2019-05-08, 最終更新日: 2023-10-04)

主引用文献

Minuesa, G.,Albanese, S.K.,Xie, W.,Kazansky, Y.,Worroll, D.,Chow, A.,Schurer, A.,Park, S.M.,Rotsides, C.Z.,Taggart, J.,Rizzi, A.,Naden, L.N.,Chou, T.,Gourkanti, S.,Cappel, D.,Passarelli, M.C.,Fairchild, L.,Adura, C.,Glickman, J.F.,Schulman, J.,Famulare, C.,Patel, M.,Eibl, J.K.,Ross, G.M.,Bhattacharya, S.,Tan, D.S.,Leslie, C.S.,Beuming, T.,Patel, D.J.,Goldgur, Y.,Chodera, J.D.,Kharas, M.G.
Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia.
Nat Commun, 10:2691-2691, 2019

PubMed Abstract: The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08-2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI's oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.

PubMed: 31217428
DOI: 10.1038/s41467-019-10523-3

実験手法

X-RAY DIFFRACTION (1.603 Å)