Structure of the M4 muscarinic acetylcholine receptor (M4-MT4L) bound to tiotropium

Structure

x-ray diffraction · 2 distinct chains · 79% helix, 0% strand (DSSP).

Ligands and binding sites

• OLA · Oleic acid · ligand · 5 copies · chains A, B
• 0HK · (1R,2R,4S,5S,7S)-7-{[hydroxy(dithiophen-2-yl)acetyl]oxy}-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0~2,4~]nonane · ligand · 2 copies · chains A, B
• EDT · {[-(bis-carboxymethyl-amino)-ethyl]-carboxymethyl-amino}-acetic acid · ligand · chains A
• OLC · (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate · additive · 5 copies · chains A, B
• P6G · Hexaethylene glycol · additive · 2 copies · chains A, B
• PG6 · 1-(2-methoxy-ethoxy)-2-{2-[2-(2-methoxy-ethoxy]-ethoxy}-ethane · additive · chains B

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

Pockets

10 pockets found on a 1 Å grid, 6 with a druggability of 0.5 or more.

Interfaces

1 interface between chains.

• A–B · 795 Ų buried · 2 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 4 disulfide (disulfide).

Compared structures

• 5DSG · Structure of the M4 muscarinic acetylcholine receptor (M4-mT4L) bound to tiotropium · the same entry in another collection · chain A against A, TM-score 1.00
• P08173 · AlphaFold monomer V2.0 prediction for muscarinic acetylcholine receptor M4 (P08173) · a predicted model of the same protein · chain B against A, TM-score 0.78

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 P08173
• Every structure of UniProt P00720
• Elsewhere: RCSB PDB 5DSG · PDBe 5DSG · UniProt P08173 · UniProt P00720