View source for 4q02


==Second-site screening of K-Ras in the presence of covalently attached first-site ligands==
<StructureSection load='4q02' size='340' side='right'caption='[[4q02]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4q02]] 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=4Q02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q02 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]] 1.702&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2XG:3,4-DIFLUOROBENZENETHIOL'>2XG</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4q02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q02 OCA], [https://pdbe.org/4q02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q02 RCSB], [https://www.ebi.ac.uk/pdbsum/4q02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q02 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== 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<ref>PMID:25087006</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4q02" style="background-color:#fffaf0;"></div>

==See Also==
*[[GTPase KRas 3D structures|GTPase KRas 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Camper DV]]
[[Category: Fesik SW]]
[[Category: Friberg A]]
[[Category: Olejniczak ET]]
[[Category: Phan J]]
[[Category: Sun Q]]