1FVY

SOLUTION STRUCTURE OF THE OSTEOGENIC 1-31 FRAGMENT OF THE HUMAN PARATHYROID HORMONE

1FVY の概要

• エントリーDOI: 10.2210/pdb1fvy/pdb
• 分子名称: PARATHYROID HORMONE (1 entity in total)
• 機能のキーワード: helix-turn-helix, parathyroid hormone, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3726.35

構造登録者

Chen, Z. (登録日: 2000-09-20, 公開日: 2000-11-22, 最終更新日: 2024-05-29)

主引用文献

Chen, Z.,Xu, P.,Barbier, J.R.,Willick, G.,Ni, F.
Solution structure of the osteogenic 1-31 fragment of the human parathyroid hormone.
Biochemistry, 39:12766-12777, 2000

PubMed Abstract: The solution conformations of a selectively osteogenic 1-31 fragment of the human parathyroid hormone (hPTH), hPTH(1-31)NH(2), have been characterized by use of very high field NMR spectroscopy at 800 MHz. The combination of the CalphaH proton and (13)Calpha chemical shifts, (3)J(NH)(alpha) coupling constants, NH proton temperature coefficients, and backbone NOEs reveals that the hPTH(1-31)NH(2) peptide has well-formed helical structures localized in two distinct segments of the polypeptide backbone. There are also many characteristic NOEs defining specific side-chain/backbone and side-chain/side-chain contacts within both helical structures. The solution structure of hPTH(1-31)NH(2) contains a short N-terminal helical segment for residues 3-11, including the helix capping residues 3 and 11 and a long C-terminal helix for residues 16-30. The two helical structures are reinforced by well-defined capping motifs and side-chain packing interactions within and at both ends of these helices. On one face of the C-terminal helix, there are side-chain pairs of Glu22-Arg25, Glu22-Lys26, and Arg25-Gln29 that can form ion-pair and/or hydrogen bonding interactions. On the opposite face of this helix, there are characteristic hydrophobic interactions involving the aromatic side chain of Trp23 packing against the aliphatic side chains of Leu15, Leu24, Lys27, and Leu28. There is also a linear array of hydrophobic residues from Val2, to Leu7, to Leu11 and continuing on to residues His14 and Leu15 in the hinge region and to Trp23 in the C-terminal helix. Capping and hydrophobic interactions at the end of the N-terminal and at the beginning of the C-terminal helix appear to consolidate the helical structures into a V-shaped overall conformation for at least the folded population of the hPTH(1-31)NH(2) peptide. Stabilization of well-folded conformations in this linear 1-31 peptide fragment and possibly other analogues of human PTH may have a significant impact on the biological activities of the PTH peptides in general and specifically for the osteogenic/anabolic activities of bone-building PTH analogues.

PubMed: 11041841
DOI: 10.1021/bi000882e

実験手法

SOLUTION NMR