ABCMdb

PMID: 20660086

Jacobson MA, Kreatsoulas C, Pascarella DM, O'Brien JA, Sur C
The M1 muscarinic receptor allosteric agonists AC-42 and 1-[1'-(2-methylbenzyl)-1,4'-bipiperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one bind to a unique site distinct from the acetylcholine orthosteric site.
Mol Pharmacol. 2010 Oct;78(4):648-57. Epub 2010 Jul 21., [PubMed]

Sentences

No. Mutations Sentence Comment

167 ABCC8 p.Tyr179Phe ABCC8 p.Tyr179Ala In comparison, the affinity of N-desmethylclozapine was only slightly changed on W101A and W101F, where a 2-fold decrease and 1.25-fold increase in potency were measured, respectively. Substitution of Tyr179 with either alanine or phenylalanine resulted in only minor changes in functional potencies -10 -9 -8 -7 -6 -5 -4 -3 0 20 40 60 80 100 Ile Phe Log [Agonist] (M) %Max -10 -9 -8 -7 -6 -5 -4 -3 0 20 40 60 80 100 Asn Gly Log [Agonist] (M) %Max -10 -9 -8 -7 -6 -5 -4 -3 0 20 40 60 80 100 Asn Thr Log [Agonist] (M) %Max Ach AC42 TBPB Fig. 4. Login to comment 173 ABCC8 p.Tyr179Phe ABCC8 p.Tyr179Ala The affinity of acetylcholine was decreased by only 2.5and 2-fold on Y179A and Y179F, respectively. Login to comment 175 ABCC8 p.Tyr179Ala The affinity for AC-42 and TBPB were increased on Y179A by 1.25and 2.9-fold, respectively. Login to comment 176 ABCC8 p.Tyr179Phe In comparison, AC-42 exhibited a 2.8-fold decrease in affinity on Y179F, whereas the affinity for TBPB was unchanged compared with wild-type M1 receptors. Login to comment