Evidence that the PTH receptor binding site on PTHrP(1-34) can hinge at Arg19/Arg20.
The structure of the biologically-active mutant of human parathyroid hormone related protein (residues 1-34) containing an Ala substituted for a His in position 9 reveals two segments of helix extending from Glu4 to Lys13 and from Phe22 to Ala34, with a reverse turn from Gln16 to Arg19. The C-terminal region contains the bulk of the PTH receptor binding site in an amphipathic helix and is capable of hinging at Arg19/Arg20. The region of the molecule containing full antagonist properties is thus confined to the C-terminal helix.
Barden
J A
JA
Sydney Institute for Biomedical Research, New South Wales, Australia.
Kemp
B E
BE
D000465:Algorithms; D000595:Amino Acid Sequence; D001120:Arginine; D001665:Binding Sites; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism*
D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D018016:Receptors, Parathyroid Hormone; C054296:parathyroid hormone-related protein (1-34); D001120:Arginine