Yonsei Med J.  2004 Jun;45(3):419-427. 10.3349/ymj.2004.45.3.419.

Structure and Function of a Minimal Receptor Activation Domain of Parathyroid Hormone

• Lee EJ
• Kim HY
• Cho MK
• Lee W
• Lim SK

• KMID: 1734123
• DOI: http://doi.org/10.3349/ymj.2004.45.3.419

Abstract

The structure and function of short-length amino terminal PTH analogues were studied. The substitution of Leu7 with Phe in [Ala3, 10Leu7Arg11]rPTH (1-11) NH2 analogue peptides did not show any reduction in cAMP formation. Replacement of the 1st, 7th and 8th residues revealed different activities, depending upon the residue type. The substitution of Ala1 by Ser in [Ala3, 10Leu7Arg11]rPTH (1-11) NH2 caused nearly a complete loss of cAMP formation. Meanwhile, NMR analysis of [ (Ala1/ Ser1) Ala3, 10 (Leu7/Phe7) Arg11]rPTH (1-11) NH2 revealed an alpha- helical backbone structure with a flexible conformation at the carboxyl-terminus. The overall results suggest that 11-residue short oligopeptide analogues of PTH tend to form an alpha-helical structure and the different activities of those analogues could be associated with residue specificity rather than the secondary conformational structure.

Keyword

Parathyroid hormone; parathyroid hormone receptor; cyclic AMP-generating activity; nuclear magnetic resonance; alpha-helix

MeSH Terms

Amino Acid Substitution
Animals
Circular Dichroism
Cyclic AMP/metabolism
Human
LLC-PK1 Cells
Nuclear Magnetic Resonance, Biomolecular
Parathyroid Hormone/*chemistry/*metabolism
Protein Structure, Secondary
Protein Structure, Tertiary
Receptor, Parathyroid Hormone, Type 1/genetics
Structure-Activity Relationship
Support, Non-U.S. Gov't
Swine