4R4C

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

4R4C の概要

• エントリーDOI: 10.2210/pdb4r4c/pdb
• 関連するPDBエントリー: 4R4I 4R4O 4R4Q 4R4T
• 分子名称: Replication protein A 70 kDa DNA-binding subunit, 5-[4-({[4-(5-carboxyfuran-2-yl)-2-chlorobenzoyl]amino}methyl)phenyl]-1-(3,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid (3 entities in total)
• 機能のキーワード: ob-fold, protein-protein interaction, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : P27694
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14108.56

構造登録者

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. (登録日: 2014-08-19, 公開日: 2014-11-19, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.4 Å)