8t5r
From Proteopedia
SOS2 crystal structure with fragment bound (compound 13)
Structural highlights
DiseaseSOS2_HUMAN Noonan syndrome. The disease is caused by mutations affecting the gene represented in this entry. FunctionSOS2_HUMAN Promotes the exchange of Ras-bound GDP by GTP.[UniProtKB:Q62245] Publication Abstract from PubMedSOS1 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. Discovery of Five SOS2 Fragment Hits with Binding Modes Determined by SOS2 X-Ray Cocrystallography.,Smith CR, Chen D, Christensen JG, Coulombe R, Fethiere J, Gunn RJ, Hollander J, Jones B, Ketcham JM, Khare S, Kuehler J, Lawson JD, Marx MA, Olson P, Pearson KE, Ren C, Tsagris D, Ulaganathan T, Van't Veer I, Wang X, Ivetac A J Med Chem. 2023 Dec 29. doi: 10.1021/acs.jmedchem.3c02140. PMID:38156904[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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