NMR study of a 34-residue N-terminal fragment of the parathyroid-hormone-related protein secreted during humoral hypercalcemia of malignancy.
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.
Barden
J A
JA
Department of Anatomy, University of Sydney, NSW, Australia.
Kemp
B E
BE
D000595:Amino Acid Sequence; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000150:complications / Q000378:metabolism*; D010281:Parathyroid Hormone; D010446:Peptide Fragments / Q000032:analysis* / Q000378:metabolism; D011487:Protein Conformation; D019379:Teriparatide
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide