4R4I

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

Summary for 4R4I

• Entry DOI: 10.2210/pdb4r4i/pdb
• Related: 4R4C 4R4O 4R4Q 4R4T
• Descriptor: Replication protein A 70 kDa DNA-binding subunit, 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 (3 entities in total)
• Functional Keywords: ob-fold, protein-protein interaction, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : P27694
• Total number of polymer chains: 1
• Total formula weight: 14116.21

Authors

Feldkamp, M.D.,Waterson, A.G.,Kennedy, J.P.,Patrone, J.D.,Pelz, N.F.,Frank, A.O.,Vangamudi, B.,Sousa-Fagundes, E.M.,Rossanese, O.W.,Fesik, S.W.,Chazin, W.J. (deposition date: 2014-08-19, release date: 2014-11-19, Last modification date: 2023-09-20)

Primary citation

Waterson, A.G.,Kennedy, J.P.,Patrone, J.D.,Pelz, N.F.,Feldkamp, M.D.,Frank, A.O.,Vangamudi, B.,Souza-Fagundes, E.M.,Rossanese, O.W.,Chazin, W.J.,Fesik, S.W.
Diphenylpyrazoles as replication protein a inhibitors.
ACS Med Chem Lett, 6:140-145, 2015

PubMed Abstract: 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.

PubMed: 25699140
DOI: 10.1021/ml5003629

Experimental method

X-RAY DIFFRACTION (1.4 Å)