Ohta K, Hayashi H, Mizuguchi H, Kagamiyama H, Fujimoto K, Fukui H
Department of Biochemistry, Osaka Medical College, Japan.
Biochem Biophys Res Commun. 1994 Sep 15;203(2):1096-101. doi: 10.1006/bbrc.1994.2295.
Based on structural comparison with other biogenic amine receptors and the histamine H2 receptor, it has been suggested that in the human histamine H1 receptor, Asp107, Thr194, and Asn198 are the residues involved in binding of histamine. We therefore used site-directed mutagenesis to investigate the roles of these three amino acid residues. Asp107 was essential for both agonist and antagonist binding. Asn198 was necessary for agonist but not for antagonist binding. Thr194 was not important for either type of binding. A good correlation was found between agonist binding and receptor activation for all the wild-type and mutant receptors. The results show that the histamine H1 receptor recognizes and is activated by histamine through the interactions of Asp107 and the amino group, and Asn198 and the imidazole ring.
基于与其他生物胺受体及组胺H2受体的结构比较，有人提出在人组胺H1受体中，Asp107、Thr194和Asn198是参与组胺结合的残基。因此，我们利用定点诱变来研究这三个氨基酸残基的作用。Asp107对激动剂和拮抗剂的结合均至关重要。Asn198是激动剂结合所必需的，但不是拮抗剂结合所必需的。Thr194对这两种类型的结合都不重要。在所有野生型和突变型受体中，激动剂结合与受体激活之间发现了良好的相关性。结果表明，组胺H1受体通过Asp107与氨基以及Asn198与咪唑环的相互作用来识别组胺并被组胺激活。
