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. Author manuscript; available in PMC: 2022 Aug 19.
Published in final edited form as: Pharmacol Rev. 2001 Dec;53(4):527–552.

TABLE 2.

Mutational analysis of the adenosine A1 with respect to ligand binding

Mutationa Species Helix/positionb Effect on Ligand Binding and Signal Transduction Reference
G14T H 1.37 Increased agonist affinity Rivkees et al., 1999a
E16A/Q H 1.39 Agonist affinity reduced 4- to 40-fold; little change antagonist affinity Barbhaiya et al., 1996
P25L H 1.48 Modest reduction of agonist affinity Rivkees et al., 1999a
I31C H 1.54 No changes in radioligand binding Rivkees et al., 1999a
C46A/S H 2.41 No changes in radioligand binding Scholl and Wells, 2000
S50A H 2.45 No changes in radioligand binding Barbhaiya et al., 1996
D55A H 2.50 Increase in agonist affinity with no change in antagonist affinity; disrupted regulation of agonist binding by sodium ions Barbhaiya et al., 1996
L65F H 2.60 No changes in radioligand binding Rivkees et al., 1999a
C80A/S H 3.25 No detectable radioligand binding Scholl and Wells, 2000
M82F H 3.27 No changes in radioligand binding Rivkees et al., 1999a
C85A H 3.30 No changes in radioligand binding Scholl and Wells, 2000
C85S Agonist affinity reduced 4- to 13-fold; no change in antagonist affinity Scholl and Wells, 2000
P86F H 3.31 Substantial reduction of agonist binding Rivkees et al., 1999a
V87A H 3.32 No change in ligand affinity Rivkees et al., 1999a
L88A H 3.33 Substantial reduction of agonist binding, but also of N-0840 antagonist binding Rivkees et al., 1999a
T91A H 3.36 Substantial reduction of agonist binding, but also of N-0840 antagonist binding Rivkees et al., 1999a
Q92A H 3.37 Substantial reduction of agonist binding, but also of N-0840 antagonist binding Rivkees et al., 1999a
S93A H 3.38 No changes in radioligand binding Barbhaiya et al., 1996
S94A H 3.39 No detectable agonist or antagonist binding Barbhaiya et al., 1996
S94T Minor changes in ligand binding Barbhaiya et al., 1996
A125K H 4.43 No changes in radioligand binding Rivkees et al., 1999a
C131A/S H 4.49 No changes in radioligand binding Scholl and Wells, 2000
S135A H 4.53 No changes in radioligand binding Barbhaiya et al., 1996
T141A H 4.59 No changes in radioligand binding Barbhaiya et al., 1996
F144L H 4.62 No changes in radioligand binding Rivkees et al., 1999a
C169A/S H No detectable radioligand binding Scholl and Wells, 2000
H251L B 6.52 Antagonist affinity reduced 4-fold; no change in agonist affinity Olah et al., 1992
C255A/S H 6.56 No changes in radioligand binding Scholl and Wells, 2000
C260A/S H No changes in radioligand binding Scholl and Wells, 2000
C263A/S H No changes in radioligand binding Scholl and Wells, 2000
I270M M270I B, C 7.35 Amino acid in position 270 contributes to canine/bovine A1 AR binding selectivity Tucker et al., 1994
T277A H 7.42 400-fold decrease in affinity of NECA with modest changes in affinity for R-PIA and S-PIA (intact cells); substantial decrease in affinity of all agonists (membranes); no change in antagonist affinity Townsend-Nicholson and Schofield, 1994; Dalpiaz et al., 1998
T277S Modest decrease in agonist affinity; no change in antagonist affinity; nature of residue in position 277 also involved in canine/bovine A1 AR binding specificity Tucker et al., 1994; Townsend-Nicholson and Schofield, 1994
H278L B 7.43 Negligible agonist and antagonist binding Olah et al., 1992
C309A/S H No changes in radioligand binding Scholl and Wells, 2000

The results were obtained from site-directed mutagenesis studies of the A1 AR (species; H, human; B, bovine; C, canine).

a

Amino acids are represented in single-letter code with position number shown. The first amino acid is that of the wild-type receptor, with the second residue being that used for substitution.

b

Position on helix, using notation of van Rhee and Jacobson (1996).