| http://purl.uniprot.org/citations/25218037 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25218037 | http://www.w3.org/2000/01/rdf-schema#comment | "Parathyroid hormone (PTH) acts via the receptor PTH1 and plays an important role in calcium homeostasis. PTH's interaction with the N-terminal domain of PTH1 is mediated in part by Arg-20 on the peptide which forms a number of interactions with the receptor: a charge-charge interaction with Asp-137; hydrogen bonds with the backbone of Asp-29 and Met-32; and hydrophobic interactions with Met-32 and Gln-37. The aim of this work was to establish the importance of the charge-charge interaction through the combined use of modified peptide ligands, site-directed mutations of the receptor, and pharmacological assays. The substitution of Arg-20 with norleucine resulted in a 50-fold reduction in potency at PTH1 and Asp-137-Glu while, in contrast, both Asp-137-Asn and Asp-137-Ala receptors were largely insensitive to this ligand modification. The effect of this removal of the positive charge as position 20 could be partially rescued at PTH1 and Asp-137-Glu, but not Asp-137-Asn and Asp-137-Ala, through a substitution of peptide position 20 with ornithine. The latter two receptors, which have no negative charge at position 137, displayed potency for PTH that was reduced by 40- and 117-fold, respectively. These data demonstrate that a negative charge at residue-137 is important for interacting with ligands containing a positive charge at residue-20, and that the Arg-20 interaction with Asp-137, observed in the crystal structure of the isolated N-terminal domain of PTH1, is likely to be present in the full length receptor where it provides an important affinity- and potency-generating interaction through a salt bridge."xsd:string |
| http://purl.uniprot.org/citations/25218037 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.peptides.2014.09.004"xsd:string |
| http://purl.uniprot.org/citations/25218037 | http://purl.uniprot.org/core/author | "Wigglesworth M.J."xsd:string |
| http://purl.uniprot.org/citations/25218037 | http://purl.uniprot.org/core/author | "Donnelly D."xsd:string |
| http://purl.uniprot.org/citations/25218037 | http://purl.uniprot.org/core/author | "Weaver R.E."xsd:string |
| http://purl.uniprot.org/citations/25218037 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25218037 | http://purl.uniprot.org/core/name | "Peptides"xsd:string |
| http://purl.uniprot.org/citations/25218037 | http://purl.uniprot.org/core/pages | "83-87"xsd:string |
| http://purl.uniprot.org/citations/25218037 | http://purl.uniprot.org/core/title | "A salt bridge between Arg-20 on parathyroid hormone (PTH) and Asp-137 on the PTH1 receptor is essential for full affinity."xsd:string |
| http://purl.uniprot.org/citations/25218037 | http://purl.uniprot.org/core/volume | "61"xsd:string |
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