4ijl

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{{STRUCTURE_4ijl| PDB=4ijl | SCENE= }}
 
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===Fragment-based Discovery of Protein-Protein Interaction Inhibitors of Replication Protein A===
 
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{{ABSTRACT_PUBMED_23914285}}
 
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==Function==
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==Fragment-based Discovery of Protein-Protein Interaction Inhibitors of Replication Protein A==
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[[http://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>
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<StructureSection load='4ijl' size='340' side='right'caption='[[4ijl]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4ijl]] 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=4IJL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IJL FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1EK:{[5-(3-CHLORO-1-BENZOTHIOPHEN-2-YL)-4-PHENYL-4H-1,2,4-TRIAZOL-3-YL]SULFANYL}ACETIC+ACID'>1EK</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ijl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ijl OCA], [https://pdbe.org/4ijl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ijl RCSB], [https://www.ebi.ac.uk/pdbsum/4ijl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ijl ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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>
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[[4ijl]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IJL OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:023914285</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 4ijl" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Single-stranded DNA-binding protein 3D structures|Single-stranded DNA-binding protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Chazin, W J.]]
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[[Category: Large Structures]]
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[[Category: Feldkamp, M D.]]
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[[Category: Chazin WJ]]
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[[Category: Fesik, S W.]]
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[[Category: Feldkamp MD]]
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[[Category: Frank, A O.]]
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[[Category: Fesik SW]]
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[[Category: Kennedy, J P.]]
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[[Category: Frank AO]]
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[[Category: Patrone, J D.]]
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[[Category: Kennedy JP]]
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[[Category: Pelz, N F.]]
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[[Category: Patrone JD]]
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[[Category: Rossanese, O W.]]
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[[Category: Pelz NF]]
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[[Category: Vangamudi, B.]]
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[[Category: Rossanese OW]]
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[[Category: Waterson, A G.]]
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[[Category: Vangamudi B]]
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[[Category: Dna binding protein-inhibitor complex]]
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[[Category: Waterson AG]]
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[[Category: Ob-fold]]
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[[Category: Protein-protein interaction]]
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Current revision

Fragment-based Discovery of Protein-Protein Interaction Inhibitors of Replication Protein A

PDB ID 4ijl

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