Table 1.
Dissociation constants arising from the binding of cAMP or cGMP to wild-type and mutant HCN2 C-termini
Construct/ligandKdKd
μMnμMnN
cAMP      
Wild type 0.09 ± 0.01 0.33 ± 0.02 1.39 ± 0.11 0.66 ± 0.09 
R591A 1.65 ± 0.57 0.35 ± 0.02 33.35 ± 5.58 0.70 ± 0.09 
T592A 0.61 ± 0.25 0.23 ± 0.01 11.83 ± 4.37 0.56 ± 0.06 
I630A 0.19 ± 0.06 0.28± 0.03 3.10 ± 0.74 0.69 ± 0.07 
D631A 0.11 ± 0.01 0.21 ± 0.02 1.90 ± 0.27 0.56 ± 0.04 
L633A 1.32 ± 0.27 0.41 ± 0.02 23.19 ± 3.29 0.69 ± 0.05 
D634A 0.10 ± 0.03 0.26 ± 0.03 1.39 ± 0.46 0.81 ± 0.03 
R635Aa 0.19 ± 0.04 0.35 ± 0.02 2.19 ± 0.40 0.45 ± 0.02 
I636A 0.47 ± 0.04 0.36 ± 0.01 6.94 ± 0.31 0.60 ± 0.03 
I636D 0.74 ± 0.29 0.56 ± 0.07 17.16 ± 2.34 0.82 ± 0.02 
K638A 0.31 ± 0.15 0.38 ± 0.04 8.00 ± 2.48 0.50 ± 0.03 
cGMP      
Wild type 0.36 ± 0.05 0.21 ± 0.01 6.13 ± 0.22 0.27 ± 0.01 
R591A 321.71 ± 26.72 2.15E-5 ± 9.20E-6   
T592A 183.53 ± 2.69 0.20 ± 0.03   
I630A 0.49 ± 0.11 0.24 ± 0.05 7.78 ± 0.31 0.44 ± 0.05 
D631A 0.21 ± 0.06 0.20 ± 0.03 4.78 ± 0.88 0.63 ± 0.09 
L633A 16.52 ± 3.20 0.74 ± 0.09   
D634A 0.54 ± 0.10 0.23 ± 0.04 8.04 ± 1.32 0.87 ± 0.14 
R635Aa 4.61 ± 0.16 0.67 ± 0.09   
I636A 0.24 ± 0.02 0.23 ± 0.01 3.23 ± 0.15 0.44 ± 0.02 
I636D 0.21 ± 0.07 0.18 ± 0.04 1.76 ± 0.51 0.56 ± 0.08 
K638A 14.69 ± 2.04 0.47 ± 0.09   
Construct/ligandKdKd
μMnμMnN
cAMP      
Wild type 0.09 ± 0.01 0.33 ± 0.02 1.39 ± 0.11 0.66 ± 0.09 
R591A 1.65 ± 0.57 0.35 ± 0.02 33.35 ± 5.58 0.70 ± 0.09 
T592A 0.61 ± 0.25 0.23 ± 0.01 11.83 ± 4.37 0.56 ± 0.06 
I630A 0.19 ± 0.06 0.28± 0.03 3.10 ± 0.74 0.69 ± 0.07 
D631A 0.11 ± 0.01 0.21 ± 0.02 1.90 ± 0.27 0.56 ± 0.04 
L633A 1.32 ± 0.27 0.41 ± 0.02 23.19 ± 3.29 0.69 ± 0.05 
D634A 0.10 ± 0.03 0.26 ± 0.03 1.39 ± 0.46 0.81 ± 0.03 
R635Aa 0.19 ± 0.04 0.35 ± 0.02 2.19 ± 0.40 0.45 ± 0.02 
I636A 0.47 ± 0.04 0.36 ± 0.01 6.94 ± 0.31 0.60 ± 0.03 
I636D 0.74 ± 0.29 0.56 ± 0.07 17.16 ± 2.34 0.82 ± 0.02 
K638A 0.31 ± 0.15 0.38 ± 0.04 8.00 ± 2.48 0.50 ± 0.03 
cGMP      
Wild type 0.36 ± 0.05 0.21 ± 0.01 6.13 ± 0.22 0.27 ± 0.01 
R591A 321.71 ± 26.72 2.15E-5 ± 9.20E-6   
T592A 183.53 ± 2.69 0.20 ± 0.03   
I630A 0.49 ± 0.11 0.24 ± 0.05 7.78 ± 0.31 0.44 ± 0.05 
D631A 0.21 ± 0.06 0.20 ± 0.03 4.78 ± 0.88 0.63 ± 0.09 
L633A 16.52 ± 3.20 0.74 ± 0.09   
D634A 0.54 ± 0.10 0.23 ± 0.04 8.04 ± 1.32 0.87 ± 0.14 
R635Aa 4.61 ± 0.16 0.67 ± 0.09   
I636A 0.24 ± 0.02 0.23 ± 0.01 3.23 ± 0.15 0.44 ± 0.02 
I636D 0.21 ± 0.07 0.18 ± 0.04 1.76 ± 0.51 0.56 ± 0.08 
K638A 14.69 ± 2.04 0.47 ± 0.09   

The table summarizes the dissociation constants (Kd) in micromoles per liter, which were determined from fitting of heat released upon binding by one or two independent site binding models as indicated. Values represent means ± SEM.

a

For R635A, the value represents the mean of four trials, three of which were taken from our previous publication (Ng et al., 2016) and another which was carried out for this study.

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