PDBsum entry 8ayh

Immune system

PDB id: 8ayh

Contents

Protein chains

648 a.a.

815 a.a.

951 a.a.

Ligands

H1H

Metals

_MG

PDB id:

8ayh

Name:

Immune system

Title:

Structure of complement c5 in complex with small molecule inhibitor and cvf

Structure:

Complement c5 beta chain. Chain: c. Fragment: beta chain, unp residues 1-675. Complement c5 alpha chain. Chain: a. Cobra venom factor. Chain: b. Synonym: cvfk,complement c3 homolog

Source:

Homo sapiens. Human. Organism_taxid: 9606. Naja kaouthia. Monocled cobra. Organism_taxid: 8649

Authors:

H.Srinivas

Key ref:

K.Jendza et al. (2019). A small-molecule inhibitor of C5 complement protein. Nat Chem Biol, 15, 666-668. PubMed id: 31209353 DOI: 10.1038/s41589-019-0303-9

Date:

02-Sep-22 Release date: 21-Dec-22

Supersedes:

6i2x

Protein chain

P01031  (CO5_HUMAN) -  Complement C5 from Homo sapiens

Seq: 1676 a.a.

Struc: 648 a.a.

Protein chain

P01031  (CO5_HUMAN) -  Complement C5 from Homo sapiens

Seq: 1676 a.a.

Struc: 815 a.a.

Protein chain

Q91132  (VCO3_NAJKA) -  Cobra venom factor from Naja kaouthia

Seq: 1642 a.a.

Struc: 951 a.a.

DOI no: 10.1038/s41589-019-0303-9

Nat Chem Biol 15:666-668 (2019)

PubMed id: 31209353

A small-molecule inhibitor of C5 complement protein.

K.Jendza, M.Kato, M.Salcius, H.Srinivas, A.De Erkenez, A.Nguyen, D.McLaughlin, C.Be, C.Wiesmann, J.Murphy, P.Bolduc, M.Mogi, J.Duca, A.Namil, M.Capparelli, V.Darsigny, E.Meredith, R.Tichkule, L.Ferrara, J.Heyder, F.Liu, P.A.Horton, M.J.Romanowski, M.Schirle, N.Mainolfi, K.Anderson, G.A.Michaud.

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.