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6DBP

RNA-recognition motif 1 of human MSI2

Summary for 6DBP
Entry DOI10.2210/pdb6dbp/pdb
DescriptorRNA-binding protein Musashi homolog 2 (2 entities in total)
Functional Keywordsmusashi2 rna recognition motif, rna binding protein
Biological sourceHomo sapiens (Human)
Total number of polymer chains2
Total formula weight19186.08
Authors
Goldgur, Y.,Kharas, M.G.,Minuesa, G. (deposition date: 2018-05-03, release date: 2019-05-08, Last modification date: 2023-10-04)
Primary citationMinuesa, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.603 Å)
Structure validation

239149

数据于2025-07-23公开中

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