8AYH

Structure of Complement C5 in Complex with small molecule inhibitor and CVF

Replaces:  6I2X

Summary for 8AYH

• Entry DOI: 10.2210/pdb8ayh/pdb
• EMDB information: 15713
• Descriptor: Complement C5 beta chain, Complement C5 alpha chain, Cobra venom factor, ... (5 entities in total)
• Functional Keywords: inhibitor, protease, complex, cryo-em, toxin, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 371446.33

Authors

Srinivas, H. (deposition date: 2022-09-02, release date: 2022-12-21, Last modification date: 2024-10-09)

Primary citation

Jendza, K.,Kato, M.,Salcius, M.,Srinivas, H.,De Erkenez, A.,Nguyen, A.,McLaughlin, D.,Be, C.,Wiesmann, C.,Murphy, J.,Bolduc, P.,Mogi, M.,Duca, J.,Namil, A.,Capparelli, M.,Darsigny, V.,Meredith, E.,Tichkule, R.,Ferrara, L.,Heyder, J.,Liu, F.,Horton, P.A.,Romanowski, M.J.,Schirle, M.,Mainolfi, N.,Anderson, K.,Michaud, G.A.
A small-molecule inhibitor of C5 complement protein.
Nat.Chem.Biol., 15:666-668, 2019

PubMed Abstract: The complement pathway is an important part of the immune system, and uncontrolled activation is implicated in many diseases. The human complement component 5 protein (C5) is a validated drug target within the complement pathway, as an anti-C5 antibody (Soliris) is an approved therapy for paroxysmal nocturnal hemoglobinuria. Here, we report the identification, optimization and mechanism of action for the first small-molecule inhibitor of C5 complement protein.

PubMed: 31209353
DOI: 10.1038/s41589-019-0303-9

Experimental method

ELECTRON MICROSCOPY (3.35 Å)