Allosteric model parameters for the interaction between R-PIA and various allosteric modulators in cell-based assays
pKB is the antilogarithm of the dissociation constant of the allosteric modulator. Log αβ is the logarithm of the composite cooperativity between the allosteric modulator and R-PIA. Log τ is the logarithm of the operational efficacy of the allosteric modulator.
| pKB | ERK 1/2 Phosphorylation | cAMP | Ca2+ | ||||
|---|---|---|---|---|---|---|---|
| Log αβ | Log τ | Log αβ | Log τ | Log αβ | Log τ | ||
| T62 | 5.49 ± 0.09 | 0.58 ± 0.06 (αβ = 3.8) | −0.32 ± 0.05 (τ = 0.5) | 0.77 ± 0.13 (αβ = 5.9) | 0.08 ± 0.06 (τ = 1.2) | 0.87 ± 0.08 (αβ = 7.4) | N.A. |
| VCP520 | 5.64 ± 0.14 | 0.57 ± 0.11 (αβ = 3.7) | −0.48 ± 0.11 (τ = 0.3) | 0.79 ± 0.07 (αβ = 6.2) | −0.18 ± 0.21 (τ = 0.7) | 1.07 ± 0.09* (αβ = 11.7) | N.A. |
| VCP333 | 5.23 ± 0.25 | 0.64 ± 0.12 (αβ = 4.4) | −1.34 ± 0.75 (τ = 0.05) | 0.91 ± 0.33 (αβ = 8.1) | 0.10 ± 0.27 (τ = 1.3) | 0.67 ± 0.13 (αβ = 4.7) | N.A. |
N.A., not applicable. Log τ fixed to −1000 since τ = 0 (ligand lacks agonism for this pathway).
↵* Statistically different (P < 0.05) from the value for ERK1/2 phosphorylation, as determined by one-way analysis of variance followed by Newman-Keuls test.