title: Structure of a novel PTH-related peptide hPTH' and its interaction with the PTH receptor.
abstract: We have previously shown that a recombinant human PTH fragment, Pro-Pro-[Arg11] hPTH (1-34)-Pro-Pro-Asp (hPTH'), could be a potentially better and more cost-effective therapeutic agent than PTH (1-34) on osteoporosis. In this report, we characterized the solution conformations of hPTH' by NMR spectroscopy and modeled the interactions between the hPTH' and the PTH receptor. By comparing it with PTH (1-34) structures and their respective interactions with the PTH receptor, we identified two segments of helix extending from Ile5 to Met8 and from Glu22 to Gln29 with a divided kink between the two helixes around Arg20. Mutated arginine makes hPTH' fill the receptor cavity better as well as forms hydrogen bonds with Val193. Understanding the ligand receptor interactions will help us design small molecules to better mimic the activities of PTH.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Kejiang
authors.initials: K
authors.lastname: Lin
authors.forename: Yonggan
authors.initials: Y
authors.lastname: Len
authors.forename: Jao
authors.initials: J
authors.lastname: Feng
authors.forename: Hongchang
authors.initials: H
authors.lastname: Gao
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
authors.forename: Donghai
authors.initials: D
authors.lastname: Lin
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D010281:Parathyroid Hormone / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000737:chemistry*
chemical_list: D010281:Parathyroid Hormone; D010446:Peptide Fragments; D044168:Receptor, Parathyroid Hormone, Type 1