Parathyroid hormone is a heparin/polyanion binding protein: binding energetics and structure modification.
The interaction of four representative polyanions with parathyroid hormone (PTH) residues 1-84 has been investigated utilizing a variety of spectroscopic and calorimetric techniques. Each of the polyanions employed demonstrate enthalpically driven binding to PTH (1-84) with significant affinity. The polyanions heparin, dextran sulfate, phytic acid, and sucrose octasulfate induce alpha-helical structure in PTH to varying extents depending on the ratio of polyanion to protein employed. Intrinsic and extrinsic fluorescence spectroscopy suggests significant protein tertiary structure alteration upon polyanion binding. Although structural modification occurred upon polyanion binding, PTH colloidal stability was increased depending on the ratio of polyanion to protein used. Nevertheless, the bioactivity of PTH in the presence of various ratios of heparin was not altered. The potential biological significance of PTH/polyanion interactions is discussed.
Kamerzell
Tim J
TJ
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
Joshi
Sangeeta B
SB
McClean
Donald
D
Peplinskie
Lori
L
Toney
Karen
K
Papac
Damon
D
Li
Meili
M
Middaugh
C Russell
CR
D002151:Calorimetry; D016264:Dextran Sulfate / Q000737:chemistry / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000737:chemistry / Q000378:metabolism*; D010833:Phytic Acid / Q000737:chemistry / Q000378:metabolism; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence; D013395:Sucrose / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
D016264:Dextran Sulfate; D006493:Heparin; D010281:Parathyroid Hormone; D010833:Phytic Acid; D000071228:Polyelectrolytes; D011108:Polymers; D013395:Sucrose; C053081:sucrose octasulfate