View source for 6uao


==Imidazole-triggered RAS-specific subtilisin SUBT_BACAM complexed with the peptide EEYSAM==
<StructureSection load='6uao' size='340' side='right'caption='[[6uao]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6uao]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_amyloliquefaciens Bacillus amyloliquefaciens] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UAO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UAO 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]] 1.63&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=6uao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uao OCA], [https://pdbe.org/6uao PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uao RCSB], [https://www.ebi.ac.uk/pdbsum/6uao PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uao ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We describe the design, kinetic properties, and structures of engineered subtilisin proteases that degrade the active form of RAS by cleaving a conserved sequence in switch 2. RAS is a signaling protein that, when mutated, drives a third of human cancers. To generate high specificity for the RAS target sequence, the active site was modified to be dependent on a cofactor (imidazole or nitrite) and protease sub-sites were engineered to create a linkage between substrate and cofactor binding. Selective proteolysis of active RAS arises from a 2-step process wherein sub-site interactions promote productive binding of the cofactor, enabling cleavage. Proteases engineered in this way specifically cleave active RAS in vitro, deplete the level of RAS in a bacterial reporter system, and also degrade RAS in human cell culture. Although these proteases target active RAS, the underlying design principles are fundamental and will be adaptable to many target proteins.

Engineering subtilisin proteases that specifically degrade active RAS.,Chen Y, Toth EA, Ruan B, Choi EJ, Simmerman R, Chen Y, He Y, Wang R, Godoy-Ruiz R, King H, Custer G, Travis Gallagher D, Rozak DA, Solomon M, Muro S, Weber DJ, Orban J, Fuerst TR, Bryan PN Commun Biol. 2021 Mar 5;4(1):299. doi: 10.1038/s42003-021-01818-7. PMID:33674772<ref>PMID:33674772</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6uao" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus amyloliquefaciens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bryan PN]]
[[Category: Orban J]]
[[Category: Toth EA]]