Cry stal structure of human parathyroid hormone 1-34 at 0.9-angstrom resolution

The N-terminal fragment 1-34 of parathyroid hormone (PTH), administered int ermittently, results in increased bone formation in patients with osteoporo sis. PTH and a related molecule, parathyroid hormone-related peptide (PTHrP ), act on cells via a common PTH/PTHrP receptor. To define more precisely t he ligand-receptor interactions, we have crystallized human PTH (hPTH)-(1-3 4) and determined the structure to 0.9-Angstrom resolution. hPTH-(1-34) cry stallizes as a slightly bent, long helical dimer, Analysis reveals that the extended helical conformation of hPTH-(1-34) is the likely bioactive confo rmation. We have developed molecular models for the interaction of hPTH-(1- 34) and hPTHrP-(1-34) with the PTH/PTHrP receptor. A receptor binding pocke t for the N terminus of hPTH-(1-34) and a hydrophobic interface with the re ceptor for the C terminus of hPTH-(1-34) are proposed.