5nxq
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the carboxy-terminal domain of yeast Ctf4 bound to a stapled Sld5 CIP== | |
| + | <StructureSection load='5nxq' size='340' side='right' caption='[[5nxq]], [[Resolution|resolution]] 2.41Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5nxq]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NXQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NXQ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=9FZ:'>9FZ</scene>, <scene name='pdbligand=9G2:'>9G2</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4c8s|4c8s]], [[4c95|4c95]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5nxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nxq OCA], [http://pdbe.org/5nxq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nxq RCSB], [http://www.ebi.ac.uk/pdbsum/5nxq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nxq ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/CTF4_YEAST CTF4_YEAST]] Accessory factor for DNA replication. It plays a role in accurately duplicating the genome in vivo. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Exploitation of synthetic lethality by small-molecule targeting of pathways that maintain genomic stability is an attractive chemotherapeutic approach. The Ctf4/AND-1 protein hub that links DNA replication, repair and chromosome segregation, represents a novel target for the synthetic lethality approach. Here we report the design, optimization, and validation of double-click stapled peptides encoding the Ctf4-interacting peptide (CIP) of the replicative helicase subunit Sld5. Screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, sub-micromolar binding to Ctf4. The mode of interaction with Ctf4 was confirmed by a crystal structure of the stapled Sld5 peptide bound to Ctf4. The stapled Sld5 peptide was able to displace the Ctf4-partner DNA polymerase alpha from the replisome in yeast extracts. Our study provides proof-of-principle evidence for the development of small-molecule inhibitors of the human-CTF4 orthologue AND-1. | ||
| - | + | Targeting the genome stability hub Ctf4 by stapled-peptide design.,Wu Y, Villa F, Maman J, Dobnikar L, Lau YH, Simon AC, Labib K, Spring DR, Pellegrini L Angew Chem Int Ed Engl. 2017 Aug 17. doi: 10.1002/anie.201705611. PMID:28815832<ref>PMID:28815832</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 5nxq" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Pellegrini, L]] | [[Category: Pellegrini, L]] | ||
[[Category: Wu, Y]] | [[Category: Wu, Y]] | ||
| + | [[Category: Adaptor protein]] | ||
| + | [[Category: Beta-propeller domain]] | ||
| + | [[Category: Dna replication]] | ||
| + | [[Category: Replication]] | ||
Revision as of 04:17, 30 August 2017
Crystal structure of the carboxy-terminal domain of yeast Ctf4 bound to a stapled Sld5 CIP
| |||||||||||
