6u9l
From Proteopedia
(Difference between revisions)
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<StructureSection load='6u9l' size='340' side='right'caption='[[6u9l]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='6u9l' size='340' side='right'caption='[[6u9l]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'> | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U9L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U9L 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]] 1.7Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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=6u9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u9l OCA], [https://pdbe.org/6u9l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u9l RCSB], [https://www.ebi.ac.uk/pdbsum/6u9l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u9l ProSAT]</span></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=6u9l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u9l OCA], [https://pdbe.org/6u9l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u9l RCSB], [https://www.ebi.ac.uk/pdbsum/6u9l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u9l ProSAT]</span></td></tr> | ||
</table> | </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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 6u9l" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Bacillus amyloliquefaciens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bryan PN]] | [[Category: Bryan PN]] | ||
[[Category: Orban J]] | [[Category: Orban J]] | ||
[[Category: Toth EA]] | [[Category: Toth EA]] | ||
Current revision
Imidazole-triggered RAS-specific subtilisin SUBT_BACAM
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