NMR solution structure of the [Ala26]parathyroid‐hormone‐related protein(1 – 34) expressed in humoral hypercalcemia of malignancy

Abstract

The structure of the biologically active N‐terminal domain of human parathyroid‐hormone‐related protein (residues 1–34) containing an Ala substituted for a His in position 26 was studied by two‐dimensional proton NMR spectroscopy. Unambiguous NMR assignments of all backbone and side‐chain hydrogens were made with the aid of totally correlated spectroscopy experiments, which provided through‐bond 1H‐1H connectivities, and NOE spectroscopy, which provided through‐space and sequential backbone connectivities. The NMR data were utilized in distance‐geometry algorithms to generate a family of structures. The major structural features include two segments of α‐helix extending from Glu4 to Lys13 and from Leu27 to Thr33, with two turns from Gln16 to Arg19 and Phe22 to His25. A salt‐bridge appears likely between Arg20 and Glu30 which may be critical for holding the receptor‐binding domain together. Copyright © 1993, Wiley Blackwell. All rights reserved