Crystal structure of the orexin-1 receptor in complex with lemborexant

Structure

x-ray diffraction · 2 distinct chains · 81% helix, 3% strand (DSSP).

Ligands and binding sites

• SOG · octyl 1-thio-beta-D-glucopyranoside · ligand · 9 copies · chains A, B
• NRK · (1~{R},2~{S})-2-[(2,4-dimethylpyrimidin-5-yl) oxymethyl]-~{N}-(5-fluoranylpyridin-2-yl)-2-(3-fluorophenyl)cyclopropane-1-carboxamide · ligand · 2 copies · chains A, B
• PGW · (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy) phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl (9Z)-octadec-9-enoate · ligand · 2 copies · chains A, B
• SO4 · Sulfate ion · ion · 4 copies · chains A, B
• PG4 · Tetraethylene glycol · additive · chains A, B

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

Pockets

9 pockets found on a 1 Å grid, 4 with a druggability of 0.5 or more.

Interfaces

1 interface between chains.

• A–B · 967 Ų buried · 2 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 2 disulfide (disulfide).

Compared structures

• 6TOT · Crystal structure of the Orexin-1 receptor in complex with lemborexant · the same entry in another collection · chain A against A, TM-score 1.00
• O43613 · AlphaFold monomer V2.0 prediction for orexin receptor type 1 (O43613) · a predicted model of the same protein · chain B against A, TM-score 0.96

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 O43613
• Elsewhere: RCSB PDB 6TOT · PDBe 6TOT · UniProt O43613