View source for 3vkx


==Structure of PCNA==
<StructureSection load='3vkx' size='340' side='right'caption='[[3vkx]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3vkx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VKX 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=T3:3,5,3TRIIODOTHYRONINE'>T3</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=3vkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vkx OCA], [https://pdbe.org/3vkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vkx RCSB], [https://www.ebi.ac.uk/pdbsum/3vkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vkx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PCNA_HUMAN PCNA_HUMAN] Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.<ref>PMID:19443450</ref> <ref>PMID:18719106</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We have discovered that triiodothyronin T3 inhibits binding of a PIP-Box sequence peptide to PCNA protein by competing for the same binding site, as evidenced by the co-crystal structure of the PCNA/T3 complex in 2.1 A resolution. Based on this observation, we have designed a novel, non-peptide small molecule PCNA inhibitor, T2AA, a T3 derivative that lacks thyroid hormone activity. T2AA inhibited interaction of PCNA/PIP-Box peptide with an IC50~ 1 muM and also PCNA and full-length p21 protein, the tightest PCNA ligand protein known to date. T2AA abolished interaction of PCNA and DNA polymerase delta in cellular chromatin. De novo DNA synthesis was inhibited by T2AA and the cells were arrested in S-phase. T2AA inhibited growth of cancer cells with induction of early apoptosis. Concurrently, Chk1 and RPA32 in the chromatin are phosphorylated, suggesting that T2AA causes DNA replication stress by stalling DNA replication forks. T2AA significantly inhibited TLS on a cisplatin-crosslinked template in cells. When cells were treated with a combination of cisplatin and T2AA, a significant increase in gammaH2AX induction and cell growth inhibition was observed.

Identification of a small molecule PCNA inhibitor that disrupts interactions with PIP-Box proteins and inhibits DNA replication.,Punchihewa C, Inoue A, Hishiki A, Fujikawa Y, Connelly M, Evison B, Shao Y, Heath R, Kuraoka I, Rodrigues P, Hashimoto H, Kawanishi M, Sato M, Yagi T, Fujii N J Biol Chem. 2012 Mar 1. PMID:22383522<ref>PMID:22383522</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3vkx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Proliferating cell nuclear antigen 3D structures|Proliferating cell nuclear antigen 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Actis M]]
[[Category: Connelly M]]
[[Category: Fujii N]]
[[Category: Hashimoto H]]
[[Category: Hishiki A]]
[[Category: Pagala V]]
[[Category: Punchihewa C]]
[[Category: Sato M]]
[[Category: Shimizu T]]
[[Category: Waddell B]]