Crystal structure of the ectodomain complex of the cgrp receptor, a class-B GPCR, reveals the site of drug antagonism

Structure

x-ray diffraction · 4 distinct chains · 45% helix, 13% strand (DSSP).

Ligands and binding sites

• 3N6 · N-{(1S)-5-amino-1-[(4-pyridin-4-ylpiperazin-1-yl) carbonyl]pentyl}-3,5-dibromo-nalpha-{[4-(2-oxo-1,4-dihydroquinazolin-3 (2H)-yl)piperidin-1-yl]carbonyl}-D-tyrosinamide · ligand · chains A, C, D
• 3N7 · N~4~-(5-cyclopropyl-1H-pyrazol-3-yl)-N~2~-1H-indazol-5-yl-6-methylpyrimidine-2,4-diamine · ligand · chains B
• SO4 · Sulfate ion · ion · chains B, C

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

Pockets

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

Interfaces

4 interfaces between chains.

• B–C · 991 Ų buried · 10 hydrogen bonds · protein-protein
• A–D · 990 Ų buried · 11 hydrogen bonds · protein-protein
• A–C · 293 Ų buried · 3 hydrogen bonds · protein-protein
• C–D · 264 Ų buried · 3 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 12 disulfide (disulfide).

Compared structures

• 3N7S · Crystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR, reveals… · the same entry in another collection · chain D against D, TM-score 1.00
• O60894 · AlphaFold monomer V2.0 prediction for receptor activity-modifying protein 1 (O60894) · a predicted model of the same protein · chain D against A, TM-score 0.96
• Q16602 · AlphaFold monomer V2.0 prediction for calcitonin gene-related peptide type 1 receptor… · a predicted model of the same protein · chain A against A, TM-score 0.95

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 Q16602
• Every structure of UniProt O60894
• Elsewhere: RCSB PDB 3N7S · PDBe 3N7S · UniProt Q16602 · UniProt O60894