Table 2.
Structural Analysis of the Deficient Mutations
| MT2 Mutants | Pwta | Pmuta | Location in 3-Dimensional Wild-Type Model | Residue Exposure | Local Effect | Putative Global Effect |
|---|---|---|---|---|---|---|
| Ala42Pro | 0.30 | 0 | Very close to extracellular region of TM1 | Protein | Gain of a kink in TM1 axis | Reorganization of helix packing impairing the native flexibility |
| Direct perturbation of the ligand binding site | ||||||
| Leu60Arg | 0.76 | 0 | Close to cytoplasmic region of TM1 | Membrane | Loss of hydrophobic protein-lipid tail contacts | Destabilization of cytoplasmic region for protein G binding |
| Gain of electrostatic protein-lipid head contacts | Stabilization of receptor impairing the native flexibility | |||||
| Pro95Leu | 0.96 | 0 | Close to extracellular region of TM2 | Membrane | Loss of a kink in TM2 axis | Penalizing change of extracellular flexibility/structure for ligand binding |
| Tyr308Ser | 1 | 0 | Very close to cytoplasmic region of TM7 | Protein | Perturbation | |
| Part of the conserved NPXXY TM7 pattern |
a
Pwt and Pmut are likelihoods at the critical positions of wild-type and mutated residues, respectively. The occurrences are deduced from 260 homologous sequences, not smaller than 75 residues and in the range 30–94% of sequence identity with the human melatonin MT2 receptor, extracted and aligned from a BLAST search (Basic local alignment search tool, [122]) against the UniRef100 database (123).