6r28
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6r28]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R28 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6r28]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R28 FirstGlance]. <br> | ||
| - | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 35 models</td></tr> |
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HCS:2-AMINO-4-MERCAPTO-BUTYRIC+ACID'>HCS</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HCS:2-AMINO-4-MERCAPTO-BUTYRIC+ACID'>HCS</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=6r28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r28 OCA], [https://pdbe.org/6r28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r28 RCSB], [https://www.ebi.ac.uk/pdbsum/6r28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r28 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=6r28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r28 OCA], [https://pdbe.org/6r28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r28 RCSB], [https://www.ebi.ac.uk/pdbsum/6r28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r28 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Aberrant Ras signalling drives 30% of cancers and inhibition of Rho family small-GTPase signalling has been shown to combat Ras-driven cancers. Here we present the discovery of a 16mer cyclic peptide that binds to Cdc42 with nanomolar affinity. Affinity maturation of this sequence has produced a panel of derived candidates with increased affinity and modulated specificity for other closely related small-GTPases. The structure of the tightest binding peptide was solved by NMR and its binding site on Cdc42 determined. Addition of a cell penetrating sequence allowed the peptides to access the cell interior and engage with their target(s), modulating signalling pathways. In Ras-driven cancer cell models, the peptides have an inhibitory effect on proliferation and show suppression of both invasion and motility. As such they represent promising candidates for Rho-family small GTPase inhibitors and therapeutics targeting Ras-driven cancers. Our data adds to the growing literature demonstrating that peptides are establishing their place in the biologics arm of drug discovery. | ||
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| + | The discovery and maturation of peptide biologics targeting the small G protein Cdc42: a bioblockade for Ras-driven signalling.,Tetley GJN, Murphy NP, Bonetto S, Ivanova-Berndt G, Revell J, Mott HR, Cooley RN, Owen D J Biol Chem. 2020 Jan 20. pii: RA119.010077. doi: 10.1074/jbc.RA119.010077. PMID:31959628<ref>PMID:31959628</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6r28" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Structure of peptide P7, which binds Cdc42 and inhibits effector interactions.
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