Small molecule inhibition of the TNF family cyokine CD40 ligand through a subunit fracture mechanism

Structure

x-ray diffraction · 3 distinct chains · 2% helix, 55% strand (DSSP).

Ligands and binding sites

• LKJ · (2R)-{[(2'-[(biphenyl-3-ylmethyl)carbamoyl]-6'-{[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]carbonyl}-6-{[(2R)-2-(1H-pyrrol-1-ylmethyl)pyrrolidin-1-yl]carbonyl}-4,4'-bipyridin-2-yl)carbonyl]amino}(cyclohexyl)ethanoic acid · ligand · chains A, B, C
• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 6 copies · chains A, B, C

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

2 pockets found on a 1 Å grid, 1 with a druggability of 0.5 or more.

Interfaces

3 interfaces between chains.

• A–B · 960 Ų buried · 12 hydrogen bonds · protein-protein
• B–C · 874 Ų buried · 10 hydrogen bonds · protein-protein
• A–C · 203 Ų buried · 2 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 3 glycan, 2 disulfide (N-glycosylation, disulfide).

Compared structures

• 3LKJ · Small Molecule Inhibition of the TNF Family Cyokine CD40 Ligand Through a Subunit… · the same entry in another collection · chain A against A, TM-score 1.00
• P29965 · AlphaFold monomer V2.0 prediction for CD40 ligand (P29965) · a predicted model of the same protein · chain A against A, TM-score 0.97

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt P29965
• Elsewhere: RCSB PDB 3LKJ · PDBe 3LKJ · UniProt P29965