Structure of a novel PTH-related peptide hPTH' and its interaction with the PTH receptor.

Abstract

We have previously shown that a recombinant human PTH fragment, Pro-Pro-[Arg11] hPTH (1-34)-Pro-Pro-Asp (hPTH'), could be a potentially better and more cost-effective therapeutic agent than PTH (1-34) on osteoporosis. In this report, we characterized the solution conformations of hPTH' by NMR spectroscopy and modeled the interactions between the hPTH' and the PTH receptor. By comparing it with PTH (1-34) structures and their respective interactions with the PTH receptor, we identified two segments of helix extending from Ile5 to Met8 and from Glu22 to Gln29 with a divided kink between the two helixes around Arg20. Mutated arginine makes hPTH' fill the receptor cavity better as well as forms hydrogen bonds with Val193. Understanding the ligand receptor interactions will help us design small molecules to better mimic the activities of PTH.

• Authors: Kejiang Lin, Yonggan Len, Jao Feng, Hongchang Gao, Qidong You, Donghai Lin, Jingjing Liu
• Journal: Journal of peptide science : an official publication of the European Peptide Society (J Pept Sci) Vol. 18 Issue 6 Pg. 413-7 (Jun 2012) ISSN: 1099-1387 [Electronic] England
• PMID: 22517776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

Chemical References

• Parathyroid Hormone
• Peptide Fragments
• Receptor, Parathyroid Hormone, Type 1

Topics

• Amino Acid Sequence
• Humans
• Models, Molecular
• Parathyroid Hormone (chemistry)
• Peptide Fragments (chemistry)
• Protein Conformation
• Receptor, Parathyroid Hormone, Type 1 (chemistry)