NMR solution structure of the [Ala26]parathyroid-hormone-related protein(1-34) expressed in humoral hypercalcemia of malignancy.
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.
Ray
F R
FR
University of Sydney, Department of Anatomy, Australia.
Barden
J A
JA
Kemp
B E
BE
D000595:Amino Acid Sequence; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000648:ultrastructure*; D010281:Parathyroid Hormone / Q000737:chemistry; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins
D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C054296:parathyroid hormone-related protein (1-34)