Stabilized NMR structure of the hypercalcemia of malignancy peptide PTHrP[Ala-26](1-34)amide

Biochim Biophys Acta. 1994 Oct 19;1208(2):256-62. doi: 10.1016/0167-4838(94)90111-2.


The structure of the biologically active mutant PTHrP[Ala-26](1-34)amide in 10% trifluoroethanol was studied by two-dimensional proton NMR spectroscopy. Complete assignments of all backbone and side chain hydrogens were made with the aid of totally correlated and nuclear Overhauser effect spectroscopy. The NMR data were utilized in the distance geometry algorithm (DIANA) and the resulting family of structures further refined using dynamic simulated annealing (X-PLOR). The major structural features include two segments of alpha-helix extending from Glu-4 to Lys-13 and from Phe-21/Phe-22 to Ala-34, with a turn from Gln-16 to Arg-19 and a hinge around Ser-14/Ile-15. A close resemblance to the structure of PTH(1-34)amide in water was noted. A comparison of the structural features common to PTH and PTHrP in different solvents was made which enabled the key structural features likely to be involved in PTH receptor binding to be identified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / analysis
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Molecular Structure
  • Parathyroid Hormone / chemistry*
  • Parathyroid Hormone-Related Protein*
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry*
  • Proteins / chemical synthesis
  • Proteins / chemistry*


  • Amino Acids
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • Proteins
  • parathyroid hormone-related protein (1-34)amide, Ala(26)-