Table IV. Parameter values for the three-state allosteric kinetic mechanism for the α7/5HT3 receptor and mutants with five equivalent ACh binding sites per molecule.
α7/5HT3 receptor parameters |
|
|
|
State parameters |
B state |
A state |
D state |
ACh on rates (M–1 s–1) | Bkon = 107 | Akon = 3.33 × 106 | Dkon = 106 |
ACh off rates (s–1) | Bkoff = 880 | Akoff = 7.5 | Dkoff = 1.6 |
Equilibrium constants (µM) |
BKD = 88 |
AKD = 2.25 |
DKD = 1.6 |
Interconversion parameters |
B↔A |
A↔D |
|
Transition state positional parameters | BAp = 0.75 | ADp = 0.99 | |
Interconversion rates (s–1) | BAk5 = 22.8 | ADk5 = 2.54 | |
ABk5 = 0.107 | DAk5 = 1.10 | ||
BAk0 = 0.233 | ADk0 = 2.5 | ||
ABk0 = 105 | DAk0 = 6.0 | ||
Allosteric constants | BAL0 = 4.3 × 105 | ADL0 = 2.4 | |
|
BAL5 = 4.7 × 10–3 |
ADL5 = 0.43 |
|
G152Ka, P193I or G152K/P193I mutant parameters |
|
|
|
State parameters |
B state |
A state |
D state |
ACh on rates (M–1 s–1) | Bkon = 107 | Akon = 3.33 × 106 | Dkon = 106 |
ACh off rates (s–1) | Bkoff = 1173.33 | Akoff = 6.66 | Dkoff = 1.42 |
Equilibrium constants (µM) |
BKD = 117 |
AKD = 2.0 |
DKD = 1.42 |
Interconversion parameters |
B↔A |
A↔D |
|
Transition state positional parameters | BAp = 0.85 | ADp = 0.99 | |
Interconversion rates (s–1) | BAk5 = 63.5 | ADk5 = 4.07 | |
ABk5 = 3.06 × 10–6 | DAk5 = 0.92 | ||
BAk0 = 3.0 | ADk0 = 4.0 | ||
ABk0 = 100 | DAk0 = 5.0 | ||
Allosteric constants | BAL0 = 33 | ADL0 = 1.30 | |
BAL5 = 4.82 × 10–8 | ADL5 = 0.226 |
aFor the G152K mutant, BKD = 33.2 µM, AKD = 1.2 µM and DKD = 0.2 µM.