. Author manuscript; available in PMC: 2019 Oct 24.

Published in final edited form as: Nature. 2019 Apr 24;569(7755):284–288. doi: 10.1038/s41586-019-1141-3

Extended Data Table 7 |. Functional data (Gi/o GloSensor) for mutants of the lateral channel.

Data were acquired with MT₁ wild-type (WT) and mutants by using GloSensor to measure Gi/o-mediated cAMP inhibition via isoproterenol stimulation. Data represent means of EC₅₀ (number of independent experiments in square brackets), represented as mean(pEC₅₀) ± s.e.m. as well as E_MAX shown as mean(%E_MAX) ± s.e.m. %E_MAX is relative to wild-type receptor in columns, and (%E_MAX*) is relative to melatonin activity in rows. Mutant effects were calculated by the change in relative activity, or log(E_MAX /EC₅₀) subtracting wild-type from mutant. ND, not determined. Dose-response curves are shown in Supplementary Figure 6.

	melatonin			ramelteon			bitopic ligand CTL 01-05-B-A05
	EC₅₀, nM [n] (pEC₅₀)	%E_MAX (%E_MAX*)	Δlog (E_MAX / EC₅₀)	EC50, nM [n] (pEC₅₀)	%E_MAX (%E_MAX*)	Δlog (E_MAX / EC₅₀)	EC₅₀, nM [n] (pEC₅₀)	%E_MAX (%E_MAX*)	Δlog (E_MAX / EC₅₀)
WT	0.0045 [23] (11.34±0.07)	100 (100)	0	0.0035 [12] (11.45±0.15)	100 (98±2)	0	0.69 [4] (9.16±0.09)	100 (124±3)	0
A158M (4.56)	no activity					ND
A190F (5.41)	0.0141 [9] (10.85±0.20)	110±4 (100)	−0.45	0.0084 [6] (11.07±0.43)	119±7 (106±6)	−0.31	5.75 [4] (8.24±0.13)	107±3 (120±3)	−0.89