6DBP
RNA-recognition motif 1 of human MSI2
Summary for 6DBP
Entry DOI | 10.2210/pdb6dbp/pdb |
Descriptor | RNA-binding protein Musashi homolog 2 (2 entities in total) |
Functional Keywords | musashi2 rna recognition motif, rna binding protein |
Biological source | Homo sapiens (Human) |
Total number of polymer chains | 2 |
Total formula weight | 19186.08 |
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 citation | 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 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: 31217428DOI: 10.1038/s41467-019-10523-3 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.603 Å) |
Structure validation
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