Solution structures of human parathyroid hormone fragments hPTH(1-34) and hPTH(1-39) and bovine parathyroid hormone fragment bPTH(1-37).
Parathyroid hormone (PTH) is involved in regulation of the calcium level in blood and has an influence on bone metabolism, thus playing a role in osteoporosis therapy. In this study, the structures of the human PTH fragments (1-34) and (1-39) as well as bovine PTH(1-37) in aqueous buffer solution under near physiological conditions were determined using two-dimensional nuclear magnetic resonance spectroscopy. The overall structure of the first 34 amino acids of these three peptides is virtually identical, exhibiting a short NH(2)-terminal and a longer COOH-terminal helix as well as a defined loop region from His14 to Ser17, stabilized by hydrophobic interactions. bPTH(1-37), which has a higher biological activity, shows a better-defined NH(2)-terminal part. In contrast to NH(2)-terminal truncations, which cause destabilization of helical structure, neither COOH-terminal truncation nor elongation significantly influences the secondary structure. Furthermore, we investigated the structure of hPTH(1-34) in 20% trifluoroethanol solution. In addition to its helix-stabilizing effect, trifluorethanol causes the loss of tertiary hydrophobic interactions.
Marx
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UC
Lehrstuhl für Biopolymere, Universität Bayreuth, Bayreuth, D-95440, Germany. ute.marxf@uni-bayreuth.de
Adermann
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K
Bayer
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Forssmann
W G
WG
Rösch
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P
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010281:Parathyroid Hormone / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D019379:Teriparatide / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D012996:Solutions; D014867:Water; D019379:Teriparatide