› 6tot

X-ray diffraction
2.22Å resolution

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

Released:
DOI: 10.2210/pdb6tot/pdb
PDB entry 6tot coloured by chain, front view.
PDB entry 6tot coloured by chain, side view.
PDB entry 6tot coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Comparison of Orexin 1 and Orexin 2 Ligand Binding Modes Using X-ray Crystallography and Computational Analysis.
Rappas M, Ali AAE, Bennett KA, Brown JD, Bucknell SJ, Congreve M, Cooke RM, Cseke G, de Graaf C, Doré AS, Errey JC, Jazayeri A, Marshall FH, Mason JS, Mould R, Patel JC, Tehan BG, Weir M, Christopher JA
J Med Chem 63 1528-1543 (2020)
PMID: 31860301

Function and Biology Details

Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-129031 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Orexin/Hypocretin receptor type 1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 336 amino acids
Theoretical weight: 38.13 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O43613 (Residues: 28-380; Coverage: 76%)
Gene name: HCRTR1
Sequence domains: 7 transmembrane receptor (rhodopsin family)

Ligands and Environments

5 bound ligands:
Ligand NRK 2 x NRK
Ligand PG4 1 x PG4
Ligand SO4 4 x SO4
Ligand SOG 9 x SOG
Ligand PGW 2 x PGW
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I24
Spacegroup: P21
Unit cell:
a: 59.725Å b: 145.715Å c: 71.703Å
α: 90° β: 112.25° γ: 90°
R-values:
R R work R free
0.207 0.206 0.239
Expression system: Spodoptera frugiperda

Quick links

Citations

4 review citations

Put a ring on it: application of small aliphatic rings in medicinal chemistry.
Bauer et al. (2021)
3 more

3 mentions without citation

G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.
Wong et al. (2023)
2 more