title: Crystal structure of human parathyroid hormone 1-34 at 0.9-A resolution.
abstract: The N-terminal fragment 1-34 of parathyroid hormone (PTH), administered intermittently, results in increased bone formation in patients with osteoporosis. PTH and a related molecule, parathyroid hormone-related peptide (PTHrP), act on cells via a common PTH/PTHrP receptor. To define more precisely the ligand-receptor interactions, we have crystallized human PTH (hPTH)-(1-34) and determined the structure to 0.9-A resolution. hPTH-(1-34) crystallizes as a slightly bent, long helical dimer. Analysis reveals that the extended helical conformation of hPTH-(1-34) is the likely bioactive conformation. We have developed molecular models for the interaction of hPTH-(1-34) and hPTHrP-(1-34) with the PTH/PTHrP receptor. A receptor binding pocket for the N terminus of hPTH-(1-34) and a hydrophobic interface with the receptor for the C terminus of hPTH-(1-34) are proposed.
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, Indiana 46285, USA.
authors.forename: L
authors.initials: L
authors.lastname: Jin
authors.forename: S L
authors.initials: SL
authors.lastname: Briggs
authors.forename: S
authors.initials: S
authors.lastname: Chandrasekhar
authors.forename: N Y
authors.initials: NY
authors.lastname: Chirgadze
authors.forename: D K
authors.initials: DK
authors.lastname: Clawson
authors.forename: R W
authors.initials: RW
authors.lastname: Schevitz
authors.forename: D L
authors.initials: DL
authors.lastname: Smiley
authors.forename: A H
authors.initials: AH
authors.lastname: Tashjian
authors.forename: F
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D010281:Parathyroid Hormone; D010446:Peptide Fragments; D018016:Receptors, Parathyroid Hormone