8T5G

SOS2 co-crystal structure with fragment bound (compound 12)

Summary for 8T5G

• Entry DOI: 10.2210/pdb8t5g/pdb
• Descriptor: Son of sevenless homolog 2, DIMETHYL SULFOXIDE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 58031.33

Authors

Gunn, R.J.,Lawson, J.D.,Ivetac, A.,Ulaganathan, T.,Coulombe, R.,Fethiere, J. (deposition date: 2023-06-13, release date: 2024-01-10, Last modification date: 2024-01-24)

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

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: 38156904
DOI: 10.1021/acs.jmedchem.3c02140

Experimental method

X-RAY DIFFRACTION (1.92 Å)