Crystal structure of human TLR8 in complex with ORN06S

Structure

x-ray diffraction · 4 distinct chains · 11% helix, 15% strand (DSSP).

Ligands and binding sites

• URI · Uridine · ligand · 4 copies · chains A, B, C, D
• 06S · O-[(2R,3S,4R,5R)-5-(2-amino-6-oxo-3,6-dihydro-9H-purin-9-yl)-2-({[(S)-({(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-hydroxy-2-[(thiophosphonooxy)methyl]tetrahydrofuran-3-yl}oxy)(sulfanyl)phosphoryl]oxy}methyl)-4-hydroxytetrahydrofuran-3-yl] dihydrogen (S)-phosphorothioate · ligand · 4 copies · chains A, B, C, D
• UPT · 1-[(2R,3aR,4R,6R,6aR)-2-hydroxy-6-(hydroxymethyl)-2-sulfidotetrahydrofuro[3,4-d][1,3,2]dioxaphosphol-4-yl]pyrimidine-2,4(1H,3H)-dione · ligand · 4 copies · chains A, B, C, D
• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 25 copies · chains A, B, C, D
• BMA · beta-D-mannopyranose · sugar · 5 copies · chains A, B, C, D
• MAN · alpha-D-mannopyranose · sugar · 4 copies · chains A, C

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

Pockets

20 pockets found on a 1 Å grid, 16 with a druggability of 0.5 or more.

Interfaces

3 interfaces between chains.

• A–B · 2353 Ų buried · 34 hydrogen bonds · protein-protein
• C–D · 2275 Ų buried · 35 hydrogen bonds · protein-protein
• A–C · 535 Ų buried · 3 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 24 disulfide, 14 glycan (disulfide, N-glycosylation).

Compared structures

• 4R09 · Crystal structure of human TLR8 in complex with ORN06S · the same entry in another collection · chain D against D, TM-score 1.00
• Q9NR97 · AlphaFold monomer V2.0 prediction for toll-like receptor 8 (Q9NR97) · a predicted model of the same protein · chain B against A, TM-score 0.99

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 Q9NR97
• Elsewhere: RCSB PDB 4R09 · PDBe 4R09 · UniProt Q9NR97