View source for 6cej


==Solution structure of a 14mer fragment of the p21 protein==
<StructureSection load='6cej' size='340' side='right'caption='[[6cej]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cej]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CEJ FirstGlance]. <br>
</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=6cej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cej OCA], [https://pdbe.org/6cej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cej RCSB], [https://www.ebi.ac.uk/pdbsum/6cej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cej ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CDN1A_HUMAN CDN1A_HUMAN] May be the important intermediate by which p53/TP53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex.<ref>PMID:8242751</ref> <ref>PMID:9106657</ref> 
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6cej" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wegener KL]]