4r4t: Difference between revisions
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==Crystal Structure of RPA70N in complex with 5-(4-((4-(5-carboxyfuran-2-yl)phenylthioamido)methyl)phenyl)-1-(3,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid== | ==Crystal Structure of RPA70N in complex with 5-(4-((4-(5-carboxyfuran-2-yl)phenylthioamido)methyl)phenyl)-1-(3,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid== | ||
<StructureSection load='4r4t' size='340' side='right' caption='[[4r4t]], [[Resolution|resolution]] 1.28Å' scene=''> | <StructureSection load='4r4t' size='340' side='right'caption='[[4r4t]], [[Resolution|resolution]] 1.28Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4r4t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R4T FirstGlance]. <br> | <table><tr><td colspan='2'>[[4r4t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R4T FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3J0:5-{4-[({[4-(5-CARBOXYFURAN-2-YL)PHENYL]CARBONOTHIOYL}AMINO)METHYL]PHENYL}-1-(3,4-DICHLOROPHENYL)-1H-PYRAZOLE-3-CARBOXYLIC+ACID'>3J0</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3J0:5-{4-[({[4-(5-CARBOXYFURAN-2-YL)PHENYL]CARBONOTHIOYL}AMINO)METHYL]PHENYL}-1-(3,4-DICHLOROPHENYL)-1H-PYRAZOLE-3-CARBOXYLIC+ACID'>3J0</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r4c|4r4c]], [[4r4i|4r4i]], [[4r4o|4r4o]], [[4r4q|4r4q]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r4c|4r4c]], [[4r4i|4r4i]], [[4r4o|4r4o]], [[4r4q|4r4q]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RPA1, REPA1, RPA70 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4r4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r4t OCA], [http://pdbe.org/4r4t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r4t RCSB], [http://www.ebi.ac.uk/pdbsum/4r4t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r4t ProSAT]</span></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=4r4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r4t OCA], [http://pdbe.org/4r4t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r4t RCSB], [http://www.ebi.ac.uk/pdbsum/4r4t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r4t ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Chazin, W J]] | [[Category: Chazin, W J]] | ||
[[Category: Feldkamp, M D]] | [[Category: Feldkamp, M D]] | ||
Revision as of 13:00, 1 May 2019
Crystal Structure of RPA70N in complex with 5-(4-((4-(5-carboxyfuran-2-yl)phenylthioamido)methyl)phenyl)-1-(3,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acidCrystal Structure of RPA70N in complex with 5-(4-((4-(5-carboxyfuran-2-yl)phenylthioamido)methyl)phenyl)-1-(3,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid
Structural highlights
Function[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.[1] [2] 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.[3] [4] Publication Abstract from PubMedReplication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). Here we describe the optimization of a diphenylpyrazole carboxylic acid series of inhibitors of these RPA-protein interactions. We evaluated substituents on the aromatic rings as well as the type and geometry of the linkers used to combine fragments, ultimately leading to submicromolar inhibitors of RPA70N protein-protein interactions. Diphenylpyrazoles as replication protein a inhibitors.,Waterson AG, Kennedy JP, Patrone JD, Pelz NF, Feldkamp MD, Frank AO, Vangamudi B, Souza-Fagundes EM, Rossanese OW, Chazin WJ, Fesik SW ACS Med Chem Lett. 2014 Nov 11;6(2):140-5. doi: 10.1021/ml5003629. eCollection, 2015 Feb 12. PMID:25699140[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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