TABLE 4

Operational allosteric ternary complex model parameters for the functional interaction between ACh and LY2033298

Parameter values are the mean ± S.E.M. from at least three experiments performed in triplicate and analyzed according to eq. 2. Logβ (β) is the logarithm of the allosteric effect on orthosteric agonist efficacy, β. Logτ_C (τ_C) is the logarithm of the corrected operational efficacy parameter, τ_C.

	Logβ (β)	Logτ_C (τ_C)
	Logβ (β)	ACh	LY2033298
M₄ WT	0.90 ± 0.03 (8)	1.84 ± 0.12 (69)	1.44 ± 0.17 (28)
M₄ D106^3.26A	0.80 ± 0.17 (6)	1.24 ± 0.11 (17)	−1000^a
M₄ W108^3.28A	1.16 ± 0.20 (14)	1.49 ± 0.17 (31)	−1000^a
M₄ L109^3.29A	1.43 ± 0.14^* (27)	1.17 ± 0.14 (15)	−1000^a
M₄ D112^3.32N	N.D.	N.D.	N.D.
M₄ D112^3.32E	2.26 ± 0.16^* (182)	−0.80 ± 0.16^* (0.2)	−1000^a
M₄ S116^3.36A	1.43 ± 0.14^* (27)	0.82 ± 0.17^* (7)	−0.35 ± 0.45^* (0.4)
M₄ N117^3.37A	1.27 ± 0.11 (19)	0.80 ± 0.27^* (6)	−0.27 ± 0.16^* (0.5)
M₄ V120^3.40A	0.80 ± 0.19 (6)	1.47 ± 0.11 (30)	1.20 ± 0.19 (16)
M₄ D129^3.49E	0.90 ± 0.09 (8)	1.45 ± 0.24 (28)	0.78 ± 0.16 (6)
M₄ D129^3.49N	1.04 ± 0.23 (11)	2.56 ± 0.39 (363)	1.86 ± 0.12 (72)

N.D., not determined.
↵a logτ_C for LY2033298 was fixed to −1000 (i.e., τ_C approaches 0) as a result of the lack of efficacy of LY2033298.
↵* p < 0.05, significantly different from WT value as determined by one-way ANOVA with Dunnett's post hoc test.