Structure of active human M2 muscarinic acetylcholine receptor bound to the agonist iperoxo and allosteric modulator LY2119620

Structure

x-ray diffraction · 2 distinct chains · 58% helix, 16% strand (DSSP).

Ligands and binding sites

• IXO · 4-(4,5-dihydro-1,2-oxazol-3-yloxy)-N,N,N-trimethylbut-2-yn-1-aminium · ligand · chains A
• 2CU · 3-amino-5-chloro-N-cyclopropyl-4-methyl-6-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy]thieno[2,3-b]pyridine-2-carboxamide · ligand · chains A

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

Pockets

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

Interfaces

1 interface between chains.

• A–B · 846 Ų buried · 8 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 3 disulfide (disulfide).

Compared structures

• 4MQT · Structure of active human M2 muscarinic acetylcholine receptor bound to the agonist… · the same entry in another collection · chain A against A, TM-score 1.00
• P08172 · AlphaFold monomer V2.0 prediction for muscarinic acetylcholine receptor M2 (P08172) · a predicted model of the same protein · chain A against A, TM-score 0.93

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 P08172
• Elsewhere: RCSB PDB 4MQT · PDBe 4MQT · UniProt P08172