Allosteric model parameters describing the cooperativity for the interaction between BETP and oxyntomodulin
α is the cooperativity factor that defines the fold change in affinity of oxyntomodulin by BETP and is calculated using a one-site competition plus allosteric modulator curve as defined in eqs. 1 and 2. αβ is the cooperativity factor that defines the fold change in receptor signaling by BETP and is a composite factor describing the combined affinity (α) and efficacy (β) modulation by the allosteric ligand. This is calculated using an operational model of agonism as defined in eqs. 3 and 4. pIC50, pEC50, and Emax values for these data sets are presented in Supplemental Table 1.
| Assay Measurement | Logα (α) | Logαβ (αβ) | Logβ (β) (Logαβ − Logα) |
|---|---|---|---|
| Binding (affinity) | 1.16 ± 0.10 (14.6)*a | - | - |
| GTPγS | 1.11 ± 0.05 (12.9)* | −0.05 ± 0.11 (0.89) | |
| cAMP | 1.10 ± 0.08 (12.6)* | −0.06 ± 0.13 (0.87) | |
| Phospho-ERK1/2 | −0.44 ± 0.19 (0.36) | −1.60 ± 0.21 (0.03)* | |
| Ca2+ | 0.23 ± 0.11 (1.70) | −0.36 ± 0.39 (0.44) | |
| β-Arrestin1 | 0.40 ± 0.08 (2.51) | −0.76 ± 0.13 (0.17) | |
| β-Arrestin2 | 0.54 ± 0.19 (3.47) | −0.62 ± 0.21 (0.24) |