Table 1.
The effect of hMC4R mutations on the agonist binding and agonist-induced cAMP accumulation.
| Mutant | NDP-MSH | THIQ | MB243 | ||||||
|---|---|---|---|---|---|---|---|---|---|
| HMC4R | IC50, nM | EC50, nM | Ratioa | IC50, nM | EC50, nM | Ratioa | IC50, nM | EC50, nM | Ratioa |
| Wild type | 2.30±0.30 | 1.70±0.61 | 1 | 2.55±0.41 | 1.75±0.33 | 1 | 30.3±5.4 | 17.21±3.4 | 1 |
| 2 | |||||||||
| E100A | 6.71±0.65b | 12.41±3.42 | 7.3 | 93.5±6.3 | 92±4 | 53 | >1000 | >1000 | >100 |
| D122A | 9.32±2.10b | 5.01±0.32 | 2.9 | 110±22 | 105±10 | 60 | >1000 | 418±30 | 24 |
| D126A | >1000b | >1000 | >1000 | >1000 | >1000 | >1000 | >1000 | >1000 | >100 |
| I129A | 1.60±0.30 | 2.14±0.15 | 1.2 | 29.9±3.1 | 15.7±4.5 | 9 | 68.5±8.3 | 58.1±5.3 | 3.4 |
| L133A | 5.10±2.00 | 0.84±0.44 | 0.49 | 8.5±2.2 | 3.74±1.74 | 2.1 | 71.3±10.2 | 20.1±1.5 | 1.2 |
| F184A | 2.94±0.61 | 1.03±0.23 | 0.6 | 1.18±0.89 | 1.32±0.53 | 0.75 | 14.5±6.8 | 4.72±0.73 | 0.27 |
| W258A | 4.01±0.13 | 2.94±0.53 | 1.7 | 9.55±2.6 | 6.24±1.26 | 3.6 | 785±23 | 357±25 | 21 |
| F261A | 3.80±0.60 | 3.35±0.21 | 2.0 | 126±11 | 107±20 | 61 | >1000 | >1000 | >100 |
| F262A | 2.30±1.70 | 1.71±0.42 | 1 | 18.9±3.4 | 7.26±1.14 | 4.1 | 520±64 | 176±15 | 10.2 |
| H264A | >1000b | 134±7 | 79 | N.D. | 19.6±2.8 | 11.2 | N.D. | 477±30 | 27.7 |
| L265A | 5.83±1.04 | 6.84±1.72 | 4.0 | 26.8±6.6 | 51.3±6.3 | 29 | 262±31 | 231±15 | 13.4 |
| Y268A | 1.87±0.90b | 3.03±0.22 | 1.8 | 6.94±2.21 | 4.93±2.51 | 2.8 | 433±85 | 153±16 | 8.9 |