TY - JOUR
T1 - Tandem sulfur-containing amino acids are epicritical determinants of dopamine D2 receptor pharmacology
AU - Schetz, John A.
AU - Sibley, David R.
PY - 2000/1/28
Y1 - 2000/1/28
N2 - The conserved aspartic acid that is required for ligand binding to the dopamine D2 receptor is followed by three tandem sulfur-containing amino acids. While previous point mutation studies did not reveal any single one of these residues as being critical for ligand binding, we now show that simultaneously substituting all three with isovolumetric, non sulfur-containing amino acids results in large decreases in the binding affinity for dopamine, (-)-raclopride and 7-(-4(4-(2,3-dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone (aripiprazole), but not for methylspiperone or allosteric modulators.
AB - The conserved aspartic acid that is required for ligand binding to the dopamine D2 receptor is followed by three tandem sulfur-containing amino acids. While previous point mutation studies did not reveal any single one of these residues as being critical for ligand binding, we now show that simultaneously substituting all three with isovolumetric, non sulfur-containing amino acids results in large decreases in the binding affinity for dopamine, (-)-raclopride and 7-(-4(4-(2,3-dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone (aripiprazole), but not for methylspiperone or allosteric modulators.
KW - Allosteric modulator
KW - Catecholamine
KW - Mutagenesis
UR - http://www.scopus.com/inward/record.url?scp=0033959797&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(99)00867-5
DO - 10.1016/S0014-2999(99)00867-5
M3 - Article
C2 - 10666514
AN - SCOPUS:0033959797
SN - 0014-2999
VL - 388
SP - R5-R7
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -