Amino acid residues involved in determining ligand interaction in the ep2 receptor

K. M. Kedzie, A. E. Donello, I. I.A. Krauss, D. F. Woodward, I. W. Regan, D. W. Gil

Research output: Contribution to journalArticlepeer-review


lho homology between prostaglandin receptors suggesls thai PG receptors ecerdiwe from an ancestral EP receptor prior to lhe development of distinct binding sites. If so. ligand selectivity should be (lett, rndned by a relatively small mmlbr of amino acid residues. Transmombrane residues thal were similar itl the EP2 and EP-t receptors but not homologous ill tire IP receptor were targeted for mutagenesis in the FP2 receptor. Activation of tile mutant receptor by an EP2 ligand AMP, IP ligand (iloprost) and P2/ll ligand (PF1) was (lelermined in a cAMP-dependent reporter gene assay. Allerati(m of a siw gle amino acid in the 7th t.ransmembrane region o[lhe El)2 receptor enhanced iloprost potency approximately i00-fold without altering the potency of P(iEI and tt:22. Mutations in other regions of the molecule did not alter potency of iloprost, and the potency of other prostglandins was not altered. Thus, we have idenlified a single amino acid change that is important for iloprost activit a1ll may have been critical in tim developmwnt of the troslacyctin binding sile.

Original languageEnglish (US)
Pages (from-to)A1163
JournalFASEB Journal
Issue number9
StatePublished - 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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