[Ligand recognition and activation mechanism of histamine H1 receptor].
Five amino acid residues of the human histamine H1 receptor that participate in histamine binding were identified using mutant H1 receptors by site-directed mutagenesis and 3D computer modeling of the receptor. The computer modeling provided two conformations of the receptor, non-active and active forms, and it was hypothesized that the binding of histamine to the receptor leads to the active state through the rewinding of the alpha-helix of TM-V. The binding sites of histamine were divided into two groups, one determined the ligand affinity and the other directly participated in the conformational change of the receptor, and the H1 antagonists bound only to the former. The mode of binding of histamine to the H1 receptor was different from those of catecholamine to the beta-receptor and of histamine to the H2 receptor.
Fukui
H
H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Ohta
K
K
Yamamoto
D
D
D001665:Binding Sites; D003198:Computer Simulation; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008024:Ligands; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D011969:Receptors, Histamine H1 / Q000502:physiology*
D008024:Ligands; D011969:Receptors, Histamine H1; D006632:Histamine