Table 3.
The effect on agonist potency of engineered mutations in or near the ligand binding pocket of the GABAB1 receptor
| Residuea | Potencyb | Agonist (assayc) | References |
|---|---|---|---|
| C187A/S | = | GABA (B, IP) | (Galvez et al., 1999; 2000a) |
| Q188A | = | GABA (B) | (Galvez et al., 1999) |
| E192A | = | GABA (B) | (Galvez et al., 2000a) |
| S246A/P/T/N | ↓↓↓ | GABA/baclofen (IP, B) | (Galvez et al., 1999; 2000a; Jensen et al., 2001a) |
| S247A | = (↑) | GABA/baclofen (IP, B) | (Galvez et al., 1999; 2000b) |
| S249A | = | GABA (B) | (Galvez et al., 1999) |
| T250A | = | GABA (B) | (Galvez et al., 1999) |
| S265A | = | GABA (IP) | (Galvez et al., 2000a) |
| Y266F | = | GABA/baclofen (IP) | (Galvez et al., 2000a) |
| S268A | = | GABA/baclofen (B, IP) | (Galvez et al., 1999; 2000b) |
| S269A | = (↓) | GABA/baclofen (B, IP) | (Galvez et al., 1999; 2000b; Jensen et al., 2001a) |
| S270A | ↓ | GABA/baclofen (B, IP) | (Galvez et al., 1999; 2000a) |
| T310A | = | GABA (B) | (Galvez et al., 1999) |
| Q312A | = | GABA/baclofen (IP, B) | (Galvez et al., 1999; 2000a) |
| Q313A | = | GABA (B) | (Galvez et al., 1999) |
| T314A | = | GABA (B) | (Galvez et al., 1999) |
| T315A | = | GABA (B) | (Galvez et al., 1999) |
| E316A | = | GABA (B) | (Galvez et al., 1999) |
| F365A | = | GABA/baclofen (IP, B) | (Galvez et al., 2000a) |
| Y366A | ↓(↓) | GABA/baclofen (IP, B) | (Galvez et al., 2000a) |
| F367A | = | GABA/baclofen (IP, B) | (Galvez et al., 2000a) |
| E458A | = | GABA (B) | (Galvez et al., 1999) |
| E459A | = | GABA (B) | (Galvez et al., 1999) |
| T460A | = | GABA (B) | (Galvez et al., 1999) |
| F463A | = | GABA/baclofen (IP) | (Galvez et al., 2000a) |
| Q464A | = | GABA (B) | (Galvez et al., 1999) |
| E465A | = (↓) | GABA (B, IP) | (Galvez et al., 2000a) |
| Y470A/F | = | GABA (IP) | (Galvez et al., 2000a) |
| D471A/E | ↓↓↓ | GABA/baclofen (IP, B) | (Galvez et al., 2000a) |
a
Numbering according to the GABAB1a variant.
b
Potency of mutant compared to wild-type receptor: ↑, 10- to 50-fold increase; =, less than 10-fold difference; ↓, 10- to 50-fold decrease or reduced binding/response; ↓↓, 50- to 500-fold decrease or weak binding/response; ↓↓↓, >500-fold decrease or no binding/response.
c
B, binding; GABAB, γ-aminobutyric acid type B; IP, inositol phosphate.