TABLE 3.
Mutational analysis of the human A2A AR with respect to ligand binding
| Mutationa | Helix/Positionb | Effect on Ligand Binding and Signal Transduction | Reference |
|---|---|---|---|
| E13Q | 1.39 | Slight reduction of agonist, but not antagonist, affinity | IJzerman et al., 1996 |
| T88A/S/R | 3.36 | Substantial decrease in agonist, but not antagonist, affinity | Jiang et al., 1996 |
| Q89A | 3.37 | Slight increase in agonist and antagonist affinity | Jiang et al., 1996 |
| Q89N/S/L | Marginal changes in ligand binding | ||
| Q89H/R | Antagonist binding affected | ||
| S90A | 3.38 | Marginal changes in ligand binding | Jiang et al., 1996 |
| S91A | 3.39 | Marginal changes in ligand binding | Jiang et al., 1996 |
| E151A/Q/D | Loss of agonist and antagonist radioligand binding | Jiang et al., 1996 | |
| E169A | ~1000-fold decrease in agonist potency | Kim et al., 1996 | |
| E169A | Gain in N6-substituted agonist affinity | Kim et al., 1996 | |
| D170K | No change in (radio)ligand binding | Kim et al., 1996 | |
| P173R | |||
| F180A | 5.41 | Minor changes in ligand binding | Kim et al., 1995 |
| N181S | 5.42 | Modest reduction of agonist binding | Kim et al., 1995 |
| F182A | 5.43 | Loss of agonist and antagonist radioligand binding | Kim et al., 1995 |
| F182Y | Modest reduction of agonist binding | Kim et al., 1995 | |
| F182W | Modest reduction of agonist binding | Kim et al., 1995 | |
| H250A | 6.52 | Loss of agonist and antagonist radioligand binding; no agonist activity in functional assays | Kim et al., 1995 |
| H250F/Y | Modest reduction of agonist binding; no effect on antagonist binding | Kim et al., 1995 | |
| N253A | 6.55 | Loss of agonist and antagonist radioligand binding | Kim et al., 1995 |
| C254A | 6.56 | Minor changes in ligand binding | Kim et al., 1995 |
| F257A | 6.59 | Loss of agonist and antagonist radioligand binding | Kim et al., 1995 |
| C262G | 6.64 | No change in radioligand binding | Kim et al., 1996 |
| I274A | 7.39 | Loss of agonist and antagonist radioligand binding; ~30-fold decrease in agonist potency | Kim et al., 1995 |
| S277A | 7.42 | Substantial decrease in agonist affinity and potency, but antagonist radioligand binding not altered | Kim et al., 1995 |
| S277T/C/N | Marginal changes in ligand binding | Jiang et al., 1996 | |
| H278A | 7.43 | Loss of agonist and antagonist radioligand binding; ~300-fold decrease in agonist potency | Kim et al., 1995 |
| H278Y | Modest reduction of agonist binding; no effect on antagonist binding | Gao et al., 2000 | |
| S281A | 7.46 | Loss of agonist and antagonist radioligand binding; no agonist activity in functional assays | Kim et al., 1995 |
| S281T | Enhanced affinity for most agonists | Kim et al., 1995 | |
| S281N | Marginal changes in ligand binding | Gao et al., 2000 |
a
Amino acids are represented in single-letter code with position number shown. The first amino acid is that of the wild-type receptor, with the second and further residues those used for substitution.
b
Position on helix, using notation of van Rhee and Jacobson (1996).