View source for 4ijh


==Fragment-based Discovery of Protein-Protein Interaction Inhibitors of Replication Protein A==
<StructureSection load='4ijh' size='340' side='right'caption='[[4ijh]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ijh]] 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=4IJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IJH 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]] 1.498&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1EJ:3-CHLORO-6-[3-(4-FLUOROPHENYL)-5-SULFANYL-4H-1,2,4-TRIAZOL-4-YL]-1-BENZOTHIOPHENE-2-CARBOXYLIC+ACID'>1EJ</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=4ijh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ijh OCA], [https://pdbe.org/4ijh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ijh RCSB], [https://www.ebi.ac.uk/pdbsum/4ijh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ijh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RFA1_HUMAN RFA1_HUMAN] Plays an essential role in several cellular processes in DNA metabolism including replication, recombination and DNA repair. Binds and subsequently stabilizes single-stranded DNA intermediates and thus prevents complementary DNA from reannealing.<ref>PMID:19116208</ref> <ref>PMID:19996105</ref>   Functions as component of the alternative replication protein A complex (aRPA). aRPA binds single-stranded DNA and probably plays a role in DNA repair; it does not support chromosomal DNA replication and cell cycle progression through S-phase. In vitro, aRPA cannot promote efficient priming by DNA polymerase alpha but supports DNA polymerase delta synthesis in the presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange.<ref>PMID:19116208</ref> <ref>PMID:19996105</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Replication Protein A (RPA) is a ssDNA binding protein that is essential for DNA replication and repair. The initiation of the DNA damage response by RPA is mediated by protein-protein interactions involving the N-terminal domain of the 70 kDa subunit with partner proteins. Inhibition of these interactions increases sensitivity towards DNA damage and replication stress and may therefore be a potential strategy for cancer drug discovery. Towards this end, we have discovered two lead series of compounds, derived from hits obtained from a fragment-based screen, that bind to RPA70N with low micromolar affinity and inhibit the binding of an ATRIP-derived peptide to RPA. These compounds may offer a promising starting point for the discovery of clinically useful RPA inhibitors.

Discovery of Protein-Protein Interaction Inhibitors of Replication Protein A.,Patrone JD, Kennedy JP, Frank AO, Feldkamp MD, Vangamudi B, Pelz NF, Rossanese OW, Waterson AG, Chazin WJ, Fesik SW ACS Med Chem Lett. 2013 Jul 11;4(7):601-605. PMID:23914285<ref>PMID:23914285</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ijh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Single-stranded DNA-binding protein 3D structures|Single-stranded DNA-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chazin WJ]]
[[Category: Feldkamp MD]]
[[Category: Fesik SW]]
[[Category: Frank AO]]
[[Category: Kennedy JP]]
[[Category: Patrone JD]]
[[Category: Pelz NF]]
[[Category: Rossanese OW]]
[[Category: Vangamudi B]]
[[Category: Waterson AG]]