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4r4i

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Revision as of 06:40, 2 March 2023

Structure of RPA70N in complex with 5-(4-((6-(5-carboxyfuran-2-yl)-1-thioxo-3,4-dihydroisoquinolin-2(1H)-yl)methyl)phenyl)-1-(3,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid

Structural highlights

4r4i is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

Replication 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.

References

↑ Mason AC, Haring SJ, Pryor JM, Staloch CA, Gan TF, Wold MS. An alternative form of replication protein a prevents viral replication in vitro. J Biol Chem. 2009 Feb 20;284(8):5324-31. doi: 10.1074/jbc.M808963200. Epub 2008, Dec 29. PMID:19116208 doi:10.1074/jbc.M808963200
↑ Kemp MG, Mason AC, Carreira A, Reardon JT, Haring SJ, Borgstahl GE, Kowalczykowski SC, Sancar A, Wold MS. An alternative form of replication protein a expressed in normal human tissues supports DNA repair. J Biol Chem. 2010 Feb 12;285(7):4788-97. doi: 10.1074/jbc.M109.079418. Epub 2009 , Dec 7. PMID:19996105 doi:10.1074/jbc.M109.079418
↑ Mason AC, Haring SJ, Pryor JM, Staloch CA, Gan TF, Wold MS. An alternative form of replication protein a prevents viral replication in vitro. J Biol Chem. 2009 Feb 20;284(8):5324-31. doi: 10.1074/jbc.M808963200. Epub 2008, Dec 29. PMID:19116208 doi:10.1074/jbc.M808963200
↑ Kemp MG, Mason AC, Carreira A, Reardon JT, Haring SJ, Borgstahl GE, Kowalczykowski SC, Sancar A, Wold MS. An alternative form of replication protein a expressed in normal human tissues supports DNA repair. J Biol Chem. 2010 Feb 12;285(7):4788-97. doi: 10.1074/jbc.M109.079418. Epub 2009 , Dec 7. PMID:19996105 doi:10.1074/jbc.M109.079418
↑ Waterson AG, Kennedy JP, Patrone JD, Pelz NF, Feldkamp MD, Frank AO, Vangamudi B, Souza-Fagundes EM, Rossanese OW, Chazin WJ, Fesik SW. Diphenylpyrazoles as replication protein a inhibitors. ACS Med Chem Lett. 2014 Nov 11;6(2):140-5. doi: 10.1021/ml5003629. eCollection, 2015 Feb 12. PMID:25699140 doi:http://dx.doi.org/10.1021/ml5003629

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4r4i"

@@ Line 3: / Line 3: @@
 <StructureSection load='4r4i' size='340' side='right'caption='[[4r4i]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4r4i]] 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=4R4I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R4I FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4r4i]] 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=4R4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R4I FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3HV:5-(4-{[6-(5-CARBOXYFURAN-2-YL)-1-THIOXO-3,4-DIHYDROISOQUINOLIN-2(1H)-YL]METHYL}PHENYL)-1-(3,4-DICHLOROPHENYL)-1H-PYRAZOLE-3-CARBOXYLIC+ACID'>3HV</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3HV:5-(4-{[6-(5-CARBOXYFURAN-2-YL)-1-THIOXO-3,4-DIHYDROISOQUINOLIN-2(1H)-YL]METHYL}PHENYL)-1-(3,4-DICHLOROPHENYL)-1H-PYRAZOLE-3-CARBOXYLIC+ACID'>3HV</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r4c|4r4c]], [[4r4o|4r4o]], [[4r4q|4r4q]], [[4r4t|4r4t]]</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=4r4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r4i OCA], [https://pdbe.org/4r4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r4i RCSB], [https://www.ebi.ac.uk/pdbsum/4r4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r4i ProSAT]</span></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=4r4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r4i OCA], [http://pdbe.org/4r4i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r4i RCSB], [http://www.ebi.ac.uk/pdbsum/4r4i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r4i ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[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>
+[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 ==
@@ Line 22: / Line 20: @@
 ==See Also==
-*[[Single-stranded DNA-binding protein|Single-stranded DNA-binding protein]]
+*[[Single-stranded DNA-binding protein 3D structures|Single-stranded DNA-binding protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chazin, W J]]
+[[Category: Chazin WJ]]
-[[Category: Feldkamp, M D]]
+[[Category: Feldkamp MD]]
-[[Category: Fesik, S W]]
+[[Category: Fesik SW]]
-[[Category: Frank, A O]]
+[[Category: Frank AO]]
-[[Category: Kennedy, J P]]
+[[Category: Kennedy JP]]
-[[Category: Patrone, J D]]
+[[Category: Patrone JD]]
-[[Category: Pelz, N F]]
+[[Category: Pelz NF]]
-[[Category: Rossanese, O W]]
+[[Category: Rossanese OW]]
-[[Category: Sousa-Fagundes, E M]]
+[[Category: Sousa-Fagundes EM]]
-[[Category: Vangamudi, B]]
+[[Category: Vangamudi B]]
-[[Category: Waterson, A G]]
+[[Category: Waterson AG]]
-[[Category: Ob-fold]]
-[[Category: Protein binding]]
-[[Category: Protein-protein interaction]]

4r4i

From Proteopedia

Revision as of 06:40, 2 March 2023

Structure of RPA70N in complex with 5-(4-((6-(5-carboxyfuran-2-yl)-1-thioxo-3,4-dihydroisoquinolin-2(1H)-yl)methyl)phenyl)-1-(3,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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