Site-Directed Mutagenesis of the Histamine H1 Receptor: Roles of Aspartic Acid107, Asparagine198 and Threonine194

Molecular determinants of ligand-directed signaling for the histamine H1 receptor

“…The model indicates the known ionic interaction between the histamine terminal amine and H 1 D3.32, about 1.7 Å apart, required for binding and activation by histamine [6,7]. Proposed hydrogen and electrostatic bonding of the histamine imidazole with H 1 residues K5.39 and N5.46, respectively, is consistent with previous studies [8].…”

Tissue Transglutaminase-Mediated Formation and Cleavage of Histamine-Gliadin Complexes: Biological Effects and Implications for Celiac Disease

“…This finding can be reconciled with the proposed interaction models of histamine with H1R and H2R. In these models, the protonated amine group of the free histamine molecules interacts with an aspartate residue in the third transmembrane domain of the receptor, an interaction that is a highly conserved feature of all aminergic receptors (19,20). TG2-mediated conjugation of histamine to glutamine residues in peptides involves the amine group of histamine and hence eliminates the possibility for protonation.…”

Domain Swapping in the Human Histamine H1Receptor

“…In these studies, coexpression of two radioligand-binding defective mutant receptors reconstituted a functional radioligand binding site, suggesting the molecular association of complementary transmembrane domains of two different defective mutant receptors. Several studies have identified critical amino acid residues in the H 1 R antagonist binding pocket (Ohta et al, 1994;Moguilevsky et al, 1998;Wieland et al, 1999 (Bakker et al, 2000). Thus, both H 1 Asp 107 Ala and H 1 Phe 432 Ala receptors can adopt a conformation allowing them to interact with H 1 R ligands.…”

“…Gifts of mianserin hydrochloride (Organon NV, Oss, The Netherlands), (R)-and (S)-cetirizine hydrochloride (UCB Pharma, Brussels, Belgium), the expression vector pcDEF 3 (Goldman et al, 1996) (Dr. J. Langer), the cDNAs encoding the human H 1 R (Fujimoto et al, 1999) (Dr. H. Fukui), the mutant human H 1 R Asp 107 Ala (Ohta et al, 1994;Moguilevsky et al, 1998) Cell Culture and Transfection. COS-7 African green monkey kidney cells were maintained at 37°C in a humidified 5% CO 2 /95% air atmosphere in Dulbecco's modified Eagle's medium containing 2 mM L-glutamine, 50 IU/ml penicillin, 50 g/ml streptomycin, and 5% (v/v) fetal calf serum.…”