Fig. 2: Ligand-binding pocket and selectivity determinants.
From: Structural basis of the ligand binding and signaling mechanism of melatonin receptors
a The ligand-binding pocket bound with the 2-iodomelatonin (yellow) in MT1 (blue). b Slab view showing the ligand access channel of MT1 in active (left) and inactive structures (right, light blue, PDB ID: 6ME4). c The ligand-binding pocket bound with the ramelteon (pink) in MT2 (green). d Slab view showing the ligand access channel of MT2 in active (left) and inactive structures (right, light cyan, PDB ID: 6ME9). e Comparison of the residues from the active (blue) and inactive (light blue) ligand-binding pockets of MT1. Red arrows indicate remarkable conformational changes. The distance between the two atoms forming the N162/Y187 hydrogen bond is 3 Å. f Comparison of the residues from the active (green) and inactive (light cyan) ligand-binding pockets of MT2. Red arrows indicate remarkable conformational changes. g 5-HEAT (cyan) docked in the active MT1. Key interacting residues from the pocket are shown as sticks. h CTL 01-05-B-A05 (salmon) docked in the active MT1. The red circle indicates the hydrophobic packing between F1945.45 and the naphthalene group. i CTL 01-05-B-A05 (salmon) docked in the active MT2. The red circle highlights the incompatible packing between I2075.45 and the naphthalene group. j Comparison of the subpockets from active MT1 (blue) and MT2 (green) bound with ramelteon (red in MT1, yellow in MT2). Key different residues are shown as sticks.
