Differding E, Gillard M, Moguilevsky N, Varsalona F, Noyer M, Daliers J, Goldstein S, Neuwels M, Lassoie M A, Guillaume J P, Bascour M, Bollen A, Hénichart J P
UCB S.A. Secteur Pharma, Drug Discovery, Chemin du Foriest, Belgique.
J Pharm Belg. 1996 May-Jun;51(3):155-60.
The binding cavity of histamine and histamine antagonists is explored using site directed mutagenesis of the human histamine H1 receptor and the amino acids involved in ligand binding are identified. Whereas Asp107 and Phe199 are important for both agonists and antagonists, two additional amino acids (Asn198 and Trp103) are required for efficient histamine binding. The binding site of antagonists is best defined as resulting from a strong ionic bond to Asp107, an orthogonal interaction between one of the aromatic rings with Phe199, and probably a hydrophobic interaction between the second aromatic ring and the lipophilic amino acids of the upper part of TMIV and TMV. This is consistent with structure-activity data of most described antagonists.
利用人组胺H1受体的定点诱变技术探索组胺及其拮抗剂的结合腔，并鉴定参与配体结合的氨基酸。虽然Asp107和Phe199对激动剂和拮抗剂都很重要，但高效组胺结合还需要另外两个氨基酸（Asn198和Trp103）。拮抗剂的结合位点最好定义为：与Asp107形成强离子键、一个芳香环与Phe199之间的正交相互作用，以及可能第二个芳香环与TMIV和TMV上部的亲脂性氨基酸之间的疏水相互作用。这与大多数已描述拮抗剂的构效关系数据一致。
