Extended Data Table 2 |. Mutation study of GABAB.
Apparent affinities for GABA (pKi) in the presence of indicated concentrations of GS39783 (0, 1, 5, 10 or 20 μM) and functional data for the GABA or GS39783 alone. N.E., no effect (absence of response); N.D., not determined (value cannot be calculated). The number of biologically independent experiments (n) is shown in parentheses.
| GB1 + GB2 | GABA pKi ± S.D. [GS] (n) | GABA pEC50 ± S.D. (n) | GS39783 pEC50 ± S.D. (n) | GS39783 Emax (% Emax GABA) ± S.D. (n) | |
|---|---|---|---|---|---|
| WT + WT | 5.44 ± 0.06 [0] (10) | 6.19 ± 0.08 (4) | 5.03 ± 0.08 (4) | 91.9 ± 4.8 (4) | |
| 5.65 ± 0.08 [1] (10) | |||||
| 5.92 ± 0.12 [5] (10) | |||||
| 5.95 ± 0.16 [10] (7) | |||||
| 6.02 ± 0.15 [20] (7) | |||||
| WT + R556A | 5.48 ± 0.07 [0] (4) | 6.16 ± 0.07 (4) | 4.93 ± 0.14 (4) | 98.5 ± 8.7 (4) | |
| 5.80 ± 0.05 [1] (4) | |||||
| 6.13 ± 0.08 [5] (4) | |||||
| 6.16 ± 0.25 [10] (4) | |||||
| 6.18 ± 0.24 [20] (4) | |||||
| WT + H647A | 5.58 ± 0.13 [0] (4) | 6.26 ± 0.09 (4) | 5.00 ± 0.11 (4) | 90.8 ± 6.6 (4) | |
| 5.79 ± 0.09 [1] (4) | |||||
| 6.12 ± 0.08 [5] (4) | |||||
| 6.06 ± 0.14 [10] (4) | |||||
| 6.15 ± 0.17 [20] (4) | |||||
| WT + L657A | 5.59 ± 0.11 [0] (4) | 6.2 ± 0.13 (4) | 5.04 ± 0.14 (4) | 99.5 ± 8.6 (4) | |
| 5.88 ± 0.07 [1] (4) | |||||
| 6.16 ± 0.06 [5] (4) | |||||
| 6.10 ± 0.16 [10] (4) | |||||
| 6.35 ± 0.14 [20] (4) | |||||
| WT+ F711A | 5.65 ± 0.16 [0] (4) | 6.3 ± 0.1 (4) | 5.14 ± 0.11 (4) | 90.7 ± 6.4 (4) | |
| 5.84 ± 0.11 [1] (4) | |||||
| Site 1 | 6.13 ± 0.14 [5] (4) | ||||
| 5.88 ± 0.26 [10] (4) | |||||
| 5.86 ± 0.23 [20] (4) | |||||
| WT + R714A | 5.46 ± 0.05 [0] (4) | 6.15 ± 0.06 (4) | 5.08 ± 0.1 (4) | 88.2 ± 5.5 (4) | |
| 5.63 ± 0.06 [1] (4) | |||||
| 5.93 ± 0.14 [5] (4) | |||||
| 5.92 ± 0.16 [10] (3) | |||||
| 5.65 ± 0.20 [20] (3) | |||||
| WT + Q720A | 5.48 ± 0.16 [0] (4) | 6.37 ± 0.07 (4) | 5.35 ± 0.11 (4) | 80.1 ± 4.7 (4) | |
| 5.70 ± 0.22 [1] (4) | |||||
| 5.96 ± 0.11 [5] (4) | |||||
| 5.82 ± 0.16 [10] (3) | |||||
| 6.03 ± 0.18 [20] (3) | |||||
| WT + SFR-AAA | 5.75 ± 0.15 [0] (4) | 6.34 ± 0.06 (4) | 5.39 ± 0.12 (4) | 93.7 ± 5.9 (4) | |
| 5.93 ± 0.08 [1] (4) | |||||
| 6.16 ± 0.10 [5] (4) | |||||
| 5.98 ± 0.18 [10] (3) | |||||
| 5.98 ± 0.19 [20] (3) | |||||
| WT + Y697A | 5.43 ± 0.04 [0] (4) | 5.56 ± 0.09 (3) | N.D. | N.D. | |
| 5.43 ± 0.10 [1] (4) | |||||
| 5.45 ± 0.05 [5] (4) | |||||
| WT+ N698A | 5.48 ± 0.07 [0] (4) | 5.96 ± 0.06 (3) | N.E. | N.E. | |
| 5.48 ± 0.05 [1] (4) | |||||
| 5.46 ± 0.07 [5] (4) | |||||
| 5.30 ± 0.16 [10] (3) | |||||
| 5.18 ± 0.16 [20] (3) | |||||
| WT + MYN-AAA* | 5.44 ± 0.05 [0] (4) | 5.25 ± 0.16 (3) | N.E. | N.E. | |
| 5.44 ± 0.05 [1] (4) | |||||
| 5.56 ± 0.18 [5] (4) | |||||
| Site 2 | M807A + WT | 5.51 ± 0.06 [0] (3) | 6.14 ± 0.06 (3) | 4.72 ± 0.12 (3) | 73.5 ± 6.6 (3) |
| 5.60 ± 0.09 [1] (3) | |||||
| 5.74 ± 0.15 [5] (3) | |||||
| Y810A + WT | 5.48 ± 0.09 [0] (3) | 5.59 ± 0.04 (3) | N.E. | N.E. | |
| 5.49 ± 0.03 [1] (3) | |||||
| 5.46 ± 0.09 [5] (3) | |||||
| N811A + WT | 5.45 ± 0.12 [0] (3) | 5.74 ± 0.03 (3) | N.E. | N.E. | |
| 5.43 ± 0.07 [1] (3) | |||||
| 5.48 ± 0.16 [5] (3) | |||||
| MYN-AAA + WT | 5.47 ± 0.10 [0] (3) | 5.12 ± 0.03 (3) | N.E. | N.E. | |
| 5.44 ± 0.09 [1] (3) | |||||
| 5.45 ± 0.11 [5] (3) |
*
Mutation MYN-AAA in GB2 refers to a triple mutant: M694A, Y697A, N698A