[English] 日本語
Yorodumi- PDB-8ayh: Structure of Complement C5 in Complex with small molecule inhibit... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ayh | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of Complement C5 in Complex with small molecule inhibitor and CVF | |||||||||
Components |
| |||||||||
Keywords | IMMUNE SYSTEM / Inhibitor / Protease / Complex / Cryo-EM / Toxin | |||||||||
Function / homology | Function and homology information Terminal pathway of complement / membrane attack complex / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / complement activation, alternative pathway / complement activation / chemokine activity / endopeptidase inhibitor activity / positive regulation of vascular endothelial growth factor production / positive regulation of chemokine production ...Terminal pathway of complement / membrane attack complex / Activation of C3 and C5 / negative regulation of macrophage chemotaxis / complement activation, alternative pathway / complement activation / chemokine activity / endopeptidase inhibitor activity / positive regulation of vascular endothelial growth factor production / positive regulation of chemokine production / Peptide ligand-binding receptors / complement activation, classical pathway / Regulation of Complement cascade / chemotaxis / G alpha (i) signalling events / toxin activity / killing of cells of another organism / cell surface receptor signaling pathway / inflammatory response / G protein-coupled receptor signaling pathway / signaling receptor binding / extracellular space / extracellular exosome / extracellular region / metal ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Naja kaouthia (monocled cobra) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.35 Å | |||||||||
Authors | Srinivas, H. | |||||||||
Funding support | Switzerland, 1items
| |||||||||
Citation | Journal: Nat Chem Biol / Year: 2019 Title: A small-molecule inhibitor of C5 complement protein. Authors: Keith Jendza / Mitsunori Kato / Michael Salcius / Honnappa Srinivas / Andrea De Erkenez / Anh Nguyen / Doug McLaughlin / Celine Be / Christian Wiesmann / Jason Murphy / Philippe Bolduc / ...Authors: Keith Jendza / Mitsunori Kato / Michael Salcius / Honnappa Srinivas / Andrea De Erkenez / Anh Nguyen / Doug McLaughlin / Celine Be / Christian Wiesmann / Jason Murphy / Philippe Bolduc / Muneto Mogi / Jose Duca / Abdel Namil / Michael Capparelli / Veronique Darsigny / Erik Meredith / Ritesh Tichkule / Luciana Ferrara / Jessica Heyder / Fang Liu / Patricia A Horton / Michael J Romanowski / Markus Schirle / Nello Mainolfi / Karen Anderson / Gregory 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 ...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. | |||||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8ayh.cif.gz | 449.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8ayh.ent.gz | 351.8 KB | Display | PDB format |
PDBx/mmJSON format | 8ayh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ayh_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 8ayh_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8ayh_validation.xml.gz | 76 KB | Display | |
Data in CIF | 8ayh_validation.cif.gz | 116.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ay/8ayh ftp://data.pdbj.org/pub/pdb/validation_reports/ay/8ayh | HTTPS FTP |
-Related structure data
Related structure data | 15713MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 73615.766 Da / Num. of mol.: 1 / Fragment: beta chain, UNP residues 1-675 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P01031 |
---|---|
#2: Protein | Mass: 112635.008 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P01031 |
#3: Protein | Mass: 184726.734 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Naja kaouthia (monocled cobra) / References: UniProt: Q91132 |
#4: Chemical | ChemComp-H1H / |
#5: Chemical | ChemComp-MG / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Complement C5-Inhibitor-CVF complex / Type: COMPLEX / Entity ID: #3 / Source: NATURAL |
---|---|
Molecular weight | Value: 0.320 MDa / Experimental value: YES |
Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 / Details: 50mM HEPES pH 7.5 100mM NaCl |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Complement C5-Inhibitor-CVF complex |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 1.4 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction | Resolution: 3.35 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 351000 / Symmetry type: POINT |