Site-directed mutagenesis of the histamine H1 receptor: roles of aspartic acid107, asparagine198 and threonine194.
Site-directed mutagenesis of the histamine H1 receptor: roles of aspartic acid107, asparagine198 and threonine194.
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组胺 H1 受体的定点诱变：天冬氨酸 107、天冬酰胺 198 和苏氨酸 194 的作用。
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
Hiroyuki Fukui
中科院分区：
文献类型：
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作者：
Kazumi Ohta;H. Hayashi;Hiroyuki Mizuguchi;Hiroyuki Kagamiyama;Katsumi Fujimoto;Hiroyuki Fukui
基于与其他生物胺受体和组胺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，我们使用定点诱变来研究这三个氨基酸残基的作用。 Asp107 对于激动剂和拮抗剂的结合都是必需的。 Asn198 对于激动剂结合是必需的，但对于拮抗剂结合不是必需的。 Thr194 对于这两种类型的结合都不重要。对于所有野生型和突变型受体，激动剂结合和受体激活之间存在良好的相关性。结果表明，组胺H1受体通过Asp107与氨基、Asn198与咪唑环的相互作用来识别并被组胺激活。
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.