8UH0
SOS2 co-crystal structure with fragment bound (compound 10)
Summary for 8UH0
| Entry DOI | 10.2210/pdb8uh0/pdb |
| Related | 8UC9 8UF2 |
| Descriptor | Son of sevenless homolog 2, 8-hydroxyquinoline-2-carbonitrile (3 entities in total) |
| Functional Keywords | sos2, nucleotide exchange factor, gef, kras, ras, signaling protein, fragment screening, fbld |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 56943.21 |
| Authors | Gunn, R.J.,Lawson, J.D. (deposition date: 2023-10-06, release date: 2024-01-10, Last modification date: 2024-03-13) |
| Primary citation | Smith, C.R.,Chen, D.,Christensen, J.G.,Coulombe, R.,Fethiere, J.,Gunn, R.J.,Hollander, J.,Jones, B.,Ketcham, J.M.,Khare, S.,Kuehler, J.,Lawson, J.D.,Marx, M.A.,Olson, P.,Pearson, K.E.,Ren, C.,Tsagris, D.,Ulaganathan, T.,Van't Veer, I.,Wang, X.,Ivetac, A. Discovery of Five SOS2 Fragment Hits with Binding Modes Determined by SOS2 X-Ray Cocrystallography. J.Med.Chem., 67:774-781, 2024 Cited by PubMed Abstract: SOS1 and SOS2 are guanine nucleotide exchange factors that mediate RTK-stimulated RAS activation. Selective SOS1:KRAS PPI inhibitors are currently under clinical investigation, whereas there are no reports to date of SOS2:KRAS PPI inhibitors. SOS2 activity is implicated in MAPK rebound when divergent SOS1 mutant cell lines are treated with the SOS1 inhibitor BI-3406; therefore, SOS2:KRAS inhibitors are of therapeutic interest. In this report, we detail a fragment-based screening strategy to identify X-ray cocrystal structures of five diverse fragment hits bound to SOS2. PubMed: 38156904DOI: 10.1021/acs.jmedchem.3c02140 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.73 Å) |
Structure validation
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