6FUJ

Complement factor D in complex with the inhibitor N-(3'-(aminomethyl)-[1,1'-biphenyl]-3-yl)-3-methylbutanamide

Summary for 6FUJ

• Entry DOI: 10.2210/pdb6fuj/pdb
• Descriptor: Complement factor D, ~{N}-[3-[3-(aminomethyl)phenyl]phenyl]-3-methyl-butanamide (3 entities in total)
• Functional Keywords: serine protease, inhibitor, complex, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 149281.87

Authors

Mac Sweeney, A.,Ostermann, N.,Vulpetti, A.,Maibaum, J.,Erbel, P.,Lorthiois, E.,Yoon, T.,Randl, S.,Ruedisser, S. (deposition date: 2018-02-27, release date: 2018-06-06, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.25 Å)