Structure of human parathyroid hormone(1-34) in the presence of solvents and micelles.
The structure of the N-terminal 34-residue fragment of human parathyroid hormone was determined in 40% trifluoroethanol employing two-dimensional 1H nuclear magnetic resonance spectroscopy. The proton chemical shifts were assigned from magnitude and phase-sensitive COSY, relayed COSY, and NOESY spectra. Distance constraints, estimated from NOESY spectra, were used to create a set of structures by distance geometry (DGEOM) which were subsequently refined by restrained energy minimization and restrained molecular dynamics (CHARMm). The resulting structures contained two helices spanning residues 3-12 and residues 17-26. The NOE constraints for residues 13-16 did not provide a single structural solution; however, their conformations were not disordered. The structures prepared by DGEOM and refined with CHARMm contained either an irregular turn or a helical structure at residues 13-16. The secondary structure of human parathyroid hormone(1-34) was also assessed by circular dichroism in the presence of methanol, trifluoroethanol, and dodecylphosphocholine micelles. Under all three conditions, the peptide formed structures containing various amounts of helical content. The formation of helical secondary structure in the presence of micelles supports the proposal that the trifluoroethanol-induced structure of human parathyroid(1-34) was not an artifact of its environment but perhaps was an indication of the conformation that the molecule adopts when in close proximity to a membrane surface and possibly when bound to the parathyroid receptor.
Allelix Biopharmaceuticals Inc., Mississauga, Ontario, Canada.
L A
LA
Strickland
R P
RP
Bozzato
K A
KA
Kronis
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D012997:Solvents; D019379:Teriparatide; D013816:Thermodynamics
D008823:Micelles; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D012997:Solvents; D019379:Teriparatide