6cix: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Lactam cyclised mimetic of a fragment of p21== | |||
<StructureSection load='6cix' size='340' side='right' caption='[[6cix]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6cix]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CIX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CIX FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6cej|6cej]], [[6civ|6civ]]</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=6cix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cix OCA], [http://pdbe.org/6cix PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cix RCSB], [http://www.ebi.ac.uk/pdbsum/6cix PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cix ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The human sliding clamp (PCNA) controls access to DNA for many proteins involved in DNA replication and repair. Proteins are recruited to the PCNA surface by means of a short, conserved peptide motif known as the PCNA-interacting protein box (PIP-box). Inhibitors of these essential protein-protein interactions may be useful as cancer therapeutics by disrupting DNA replication and repair in these highly proliferative cells. PIP-box peptide mimetics have been identified as a potentially rapid route to potent PCNA inhibitors. Here we describe the rational design and synthesis of the first PCNA peptidomimetic ligands, based on the high affinity PIP-box sequence from the natural PCNA inhibitor p21. These mimetics incorporate covalent i,i+4 side-chain/side-chain lactam linkages of different lengths, designed to constrain the peptides into the 310-helical structure required for PCNA binding. NMR studies confirmed that while the unmodified p21 peptide had little defined structure in solution, mimetic ACR2 pre-organised into 310-helical structure prior to interaction with PCNA. ACR2 displayed higher affinity binding than most known PIP-box peptides, and retains the native PCNA binding mode, as observed in the co-crystal structure of ACR2 bound to PCNA. This study offers a promising new strategy for PCNA inhibitor design for use as anti-cancer therapeutics. | |||
Rational design of a 310-helical PIP-box mimetic targeting PCNA - the human sliding clamp.,Wegener KL, McGrath AE, Dixon NE, Oakley AJ, Scanlon DB, Abell AD, Bruning J Chemistry. 2018 Jun 19. doi: 10.1002/chem.201801734. PMID:29917264<ref>PMID:29917264</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6cix" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Wegener, K L]] | |||
[[Category: Biosynthetic protein]] | |||
[[Category: Constrained]] | |||
[[Category: P21]] | |||
[[Category: Peptidomimetic]] | |||
[[Category: Pip-box motif]] | |||
Revision as of 07:13, 4 July 2018
Lactam cyclised mimetic of a fragment of p21
| ||||||||||||
