Extended Data Table 1 |. Ligand affinity data for MT2 mutants.
Mutant | melatonin | 2-pmt | ramelteon | agomelatine |
---|---|---|---|---|
Kd, nM [n] (pKd ±s.e.m.) |
Ki, nM [n] (pKi ±s.e.m.) |
Ki, nM [n] (pKi ±s.e.m.) |
Ki, nM [n] (pKi ±s.e.m.) |
|
WT | 0.54
[10] (9.27±0.12) |
0.17
[10] (9.78±0.11) |
0.23
[4] (9.66±0.10) |
0.24
[4] (9.63±0.08) |
WT + NaCI | 1.56 [6] (8.81 ± 0.18) |
ND | ND | ND |
MT2-CC (Sf9) | 63.10
[3] (7.20±0.06) |
3.14
[4] (8.50±0.06) |
2.60
[4] (8.59±0.02) |
6.88 [4] (8.16± 0.05) |
MT2-CC (sf9) + NaCI | 48.23
[3] (7.32±0.03) |
ND | ND | ND |
MT2-CC-N862.50D (Sf9) | 29.40
[6] (7.53±0.34) |
6.46
[4] (8.19±0.15) |
7.37
[4] (8.13±0.09) |
26.76
[4] (7.57±0.05) |
MT2-CC-H2085.46A (Sf9) | 10.81
[6] (7.97±0.16) |
3.57
[6] (8.45±0.03) |
2.03
[6] (8.69±0.13) |
4.98
[6] (8.30±0.04) |
D86N (2.50) | 5.80
[3] (8.24±0.04) |
0.33
[3] (9.48±0.12) |
ND | ND |
D86N (2.50) + NaCI | 3.26
[3] (8.49±0.09) |
ND | ND | ND |
L108F (ECL1) | 0.94 [3] (9.03±0.11) |
0.13 [3] (9.87±0.15) |
ND | ND |
F129W (3.41) | 2.84 [3] (8.55±0.04) |
0.22 [3] (9.65±0.08) |
ND | ND |
N137D (3.49) | 1.24 [3] (8.91±0.13) |
0.12 [3] (9.92±0.00) |
ND | ND |
C140L (3.52) | 0.21
[3] (9.68±0.05) |
0.03
[3] (10.50±0.02) |
ND | ND |
W264F (6.48) | 0.88
[3] (9.06±0.14) |
0.06
[3] (10.25±0.26) |
ND | ND |
A305P (7.50) | 3.94
[3] (8.40±0.19) |
0.47
[3] (9.32±0.06) |
ND | ND |
N312D (7.57) | 2.85
[3] (8.54±0.07) |
0.36
[3] (9.44±0.04) |
ND | ND |
P95A (2.59) | No specific binding up to 7 nM [3H]-melatonin | |||
M120A(3.32) | 0.44
[3] (9.42±0.16) |
0.028
[3] (10.7±0.3) |
0.055
[3] (10.28±0.09) |
0.052
[3] (10.35±0.18) |
N175A(4.60) | 0.86 [3] (9.2±0.3) |
0.09
[3] (10.06±0.06) |
0.08
[3] (10.12±0.11) |
0.25
[3] (9.60±0.04) |
F192A (ECL2) | Low expression, no specific binding up to 7 nM [3H]-melatonin | |||
F192I (ECL2) | No specific binding up to 7 nM [3H]-melatonin | |||
Q194A (ECL2) | 0.62 [3] (9.4±0.3) |
0.043
[3] (10.38±0.07) |
0.051
[3] (10.4±0.2) |
0.12
[3] (9.94±0.09) |
Y200A (5.38) | 0.63 [3] (9.3±0.3) |
0.14
[3] (9.86±0.01) |
0.19
[3] (9.73±0.03) |
0.67
[3] (9.18±0.02) |
A203F(5.41) | 0.82
[5] (9.09±0.01) |
0.12
[5] (9.94±0.06) |
0.19
[5] (9.47±0.19) |
0.42
[5] (9.37±0.19) |
H208A (5.46) | 1.24
[3] (8.94±0.13) |
0.17
[3] (9.79±0.09) |
0.18
[3] (9.77±0.11) |
0.22
[3] (9.68±0.11) |
N268A (6.52) | 0.96 [3] (9.3±0.4) |
0.09
[3] (10.08±0.09) |
0.12
[3] (9.92±0.05) |
0.20
[3] (9.69±0.03) |
Y294A (7.39) | 1.07
[3] (8.99±0.09) |
0.042
[3] (10.38±0.04) |
0.049
[3] (10.33±0.09) |
0.10
[3] (10.04±0.10) |
Y308S (7.53) | No specific binding up to 7 nM [3H]-melatonin |