View source for 9bvi


==Identification of multiple ligand hotspots on SOS2, compound 2==
<StructureSection load='9bvi' size='340' side='right'caption='[[9bvi]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9bvi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BVI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.787&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1ASW:4-[[4-(4-methylpiperazin-1-yl)quinazolin-2-yl]amino]phenol'>A1ASW</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9bvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bvi OCA], [https://pdbe.org/9bvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bvi RCSB], [https://www.ebi.ac.uk/pdbsum/9bvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bvi ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SOS2_HUMAN SOS2_HUMAN] Noonan syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/SOS2_HUMAN SOS2_HUMAN] Promotes the exchange of Ras-bound GDP by GTP.[UniProtKB:Q62245]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Son of Sevenless (SOS) protein family includes two highly homologous proteins, SOS1 and SOS2, that act as guanine nucleotide exchange factors (GEFs) for RAS proteins. They catalyze the GDP-to-GTP exchange, resulting in an increase of the active GTP-bound form of RAS. Despite highly similar structures and expression patterns, SOS1 is generally accepted as the dominant RAS GEF for downstream signaling in pathological states. Nonetheless, SOS2 has been reported to critically impact the RAS-PI3K/AKT signaling axis, especially in KRAS-driven cancer cell lines and in the absence of SOS1. Hence, therapeutic targeting of SOS2 may be an attractive strategy to target RAS-driven malignancies. Herein, we report the discovery and initial optimization of a selective quinazoline-based compound series that binds with micromolar affinity to the catalytic site of SOS2. We also disclose an additional, previously unreported binding site on SOS2 occupied by a different small molecule class.

Discovery of Small Molecules that Bind to Son of Sevenless 2 (SOS2).,Zak KM, Waterson AG, Geist L, Braun N, Hauer K, Rumpel K, Ramharter J, Stadtmueller H, Wolkerstorfer B, Schoenbauer D, Cui J, Phan J, Abbott JR, Sarkar D, Hodges TR, Arnold A, Sensintaffar JL, Fesik SW, Kessler D J Med Chem. 2025 Jan 17. doi: 10.1021/acs.jmedchem.4c02007. PMID:39818983<ref>PMID:39818983</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9bvi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fesik SW]]
[[Category: Phan J]]