4q02

Second-site screening of K-Ras in the presence of covalently attached first-site ligands

spinqualitylabelsall models 4q02, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4q02 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.702Å Ligands: 2XG, GDP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed K-Ras is a well-validated cancer target but is considered to be "undruggable" due to the lack of suitable binding pockets. We previously discovered small molecules that bind weakly to K-Ras but wanted to improve their binding affinities by identifying ligands that bind near our initial hits that we could link together. Here we describe an approach for identifying second site ligands that uses a cysteine residue to covalently attach a compound for tight binding to the first site pocket followed by a fragment screen for binding to a second site. This approach could be very useful for targeting Ras and other challenging drug targets. A method for the second-site screening of K-Ras in the presence of a covalently attached first-site ligand.,Sun Q, Phan J, Friberg AR, Camper DV, Olejniczak ET, Fesik SW J Biomol NMR. 2014 Sep;60(1):11-4. doi: 10.1007/s10858-014-9849-8. Epub 2014 Aug , 3. PMID:25087006 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also GTPase KRas 3D structures

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