Site-directed mutagenesis of the histamine H1 receptor: roles of aspartic acid107, asparagine198 and threonine194

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Asparagine*
  • Aspartic Acid*
  • Base Sequence
  • CHO Cells
  • Cricetinae
  • Gene Expression
  • Histamine / pharmacology
  • Humans
  • Inositol Phosphates / metabolism
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed*
  • Pyrilamine / metabolism
  • Receptors, Histamine H1 / chemistry*
  • Receptors, Histamine H1 / genetics*
  • Receptors, Histamine H1 / physiology
  • Structure-Activity Relationship
  • Threonine*


  • Inositol Phosphates
  • Receptors, Histamine H1
  • Threonine
  • Aspartic Acid
  • Asparagine
  • Histamine
  • Pyrilamine