NMR study of a 34-residue N-terminal fragment of the parathyroid-hormone-related protein secreted during humoral hypercalcemia of malignancy.

Abstract

The proton resonances of the biologically active peptide parathyroid-hormone-related protein (residues 1-34) were assigned using one-dimensional spin-decoupling techniques, two-dimensional correlated spectroscopy and by comparing the spectra of the peptides 1-20, 1-25, 1-29, 7-34 and 15-34. The conformation of 1-34 was determined using one- and two-dimensional nuclear Overhauser enhancement spectroscopy in the rotating frame. Amide proton temperature coefficients, vicinal coupling constants and circular dichroic spectra helped reveal a surprisingly compact structure with residues 3-9 forming alpha-helix, type-I beta-turns between residues 10-13 and 16-19 and several interactions between the N-terminal residues and the C-terminal residues. Of these latter, the strongest appeared to be between Asp-10 and Phe-22. One peptide surface in the deduced model presents multiple positive charges, while the opposite surface has a hydrophobic character possibly functioning to exclude water from the binding interface and enhancing the binding constant.

• Authors: J A Barden, B E Kemp
• Journal: European journal of biochemistry (Eur J Biochem) Vol. 184 Issue 2 Pg. 379-94 (Sep 15 1989) ISSN: 0014-2956 [Print] England
• PMID: 2792105 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Parathyroid Hormone
• Peptide Fragments
• Teriparatide

Topics

• Amino Acid Sequence
• Humans
• Hypercalcemia (etiology, metabolism)
• Magnetic Resonance Spectroscopy (methods)
• Models, Molecular
• Molecular Sequence Data
• Neoplasms (complications, metabolism)
• Parathyroid Hormone
• Peptide Fragments (analysis, metabolism)
• Protein Conformation
• Teriparatide