NMR solution structure of the [Ala26]parathyroid‐hormone‐related protein(1 – 34) expressed in humoral hypercalcemia of malignancy
- 1 January 1993
- journal article
- Published by Wiley in European Journal of Biochemistry
- Vol. 211 (1-2) , 205-211
- https://doi.org/10.1111/j.1432-1033.1993.tb19887.x
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 alpha-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.Keywords
This publication has 25 references indexed in Scilit:
- Investigation of the solution structure of the human parathyroid hormone fragment (1-34) by proton NMR spectroscopy, distance geometry, and molecular dynamics calculationsBiochemistry, 1991
- Efficient computation of three-dimensional protein structures in solution from nuclear magnetic resonance data using the program DIANA and the supporting programs CALIBA, HABAS and GLOMSAJournal of Molecular Biology, 1991
- NMR study of a 34‐residue N‐terminal fragment of the parathyroid‐hormone‐related protein secreted during humoral hypercalcemia of malignancyEuropean Journal of Biochemistry, 1989
- Protein Structure Determination in Solution by Nuclear Magnetic Resonance SpectroscopyScience, 1989
- The MIDAS display systemJournal of Molecular Graphics, 1988
- Synthetic human parathyroid hormone-like protein stimulates bone resorption and causes hypercalcemia in rats.Journal of Clinical Investigation, 1988
- A Parathyroid Hormone-Related Protein Implicated in Malignant Hypercalcemia: Cloning and ExpressionScience, 1987
- N-Terminal amino acid sequence of two novel tumor-derived adenylate cyclase-stimulating proteins: Identification of parathyroid hormone-like and parathyroid hormone-unlike domainsBiochemical and Biophysical Research Communications, 1987
- MLEV-17-based two-dimensional homonuclear magnetization transfer spectroscopyJournal of Magnetic Resonance (1969), 1985
- Calibration of the angular dependence of the amide proton-Cα proton coupling constants, 3JHNα, in a globular proteinJournal of Molecular Biology, 1984