INVESTIGATION OF THE SOLUTION STRUCTURE OF THE HUMAN PARATHYROID-HORMONE FRAGMENT (1-34) BY H-1-NMR SPECTROSCOPY, DISTANCE GEOMETRY, AND MOLECULAR-DYNAMICS CALCULATIONS

The structure of human parathyroid hormone fragment (1-34) in a solvent mixture of water and trifluoroethanol has been determined by H-1 nuclear magnetic resonance spectroscopy and a combination of distance geometry and molecular dynamic simulations. After complete assignment of the H-1 signals, the nuclear Overhauser enhancement data imply the existence of two a-helices, comprising residues 3-9 and 17-28, joined by a nonstructured region. The absence of any long-range NOEs and the relative magnitudes of the sequential NOEs and the 3J(H(N)H-alpha) values reflect an inherent flexibility within the entire fragment. The final structures refined by molecular dynamics further support the above results and allow discussion of structural-activity relationships.