6FUG

Complement factor D in complex with the inhibitor 3-((3-((3-(aminomethyl)phenyl)amino)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)amino)phenol

6FUG の概要

• エントリーDOI: 10.2210/pdb6fug/pdb
• 分子名称: Complement factor D, 3-[[3-[[3-(aminomethyl)phenyl]amino]-1~{H}-pyrazolo[3,4-d]pyrimidin-4-yl]amino]phenol (3 entities in total)
• 機能のキーワード: serine protease, inhibitor, complex, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 150518.97

構造登録者

Mac Sweeney, A.,Ostermann, N.,Vulpetti, A.,Maibaum, J.,Erbel, P.,Lorthiois, E.,Yoon, T.,Randl, S.,Ruedisser, S. (登録日: 2018-02-27, 公開日: 2018-06-06, 最終更新日: 2024-11-13)

主引用文献

Vulpetti, A.,Ostermann, N.,Randl, S.,Yoon, T.,Mac Sweeney, A.,Cumin, F.,Lorthiois, E.,Rudisser, S.,Erbel, P.,Maibaum, J.
Discovery and Design of First Benzylamine-Based Ligands Binding to an Unlocked Conformation of the Complement Factor D.
ACS Med Chem Lett, 9:490-495, 2018

PubMed Abstract: Complement Factor D, a serine protease of the S1 family and key component of the alternative pathway amplification loop, represents a promising target for the treatment of several prevalent and rare diseases linked to the innate immune system. Previously reported FD inhibitors have been shown to bind to the FD active site in its self-inhibited conformation characterized by the presence of a salt bridge at the bottom of the S1 pocket between Asp189 and Arg218. We report herein a new set of small-molecule FD ligands that harbor a basic S1 binding moiety directly binding to the carboxylate of Asp189, thereby displacing the Asp189-Arg218 ionic interaction and significantly changing the conformation of the self-inhibitory loop.

PubMed: 29795765
DOI: 10.1021/acsmedchemlett.8b00104

実験手法

X-RAY DIFFRACTION (2.21 Å)