2B4N

Solution Structure of Glucose-Dependent Insulinotropic Polypeptide

2B4N の概要

• エントリーDOI: 10.2210/pdb2b4n/pdb
• 分子名称: Gastric inhibitory polypeptide (1 entity in total)
• 機能のキーワード: gip, molecular modelling, helix, diabetes, obesity, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P09681
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4990.59

構造登録者

Alana, I.,Hewage, C.M.,O'Harte, F.P.M.,Malthouse, J.P.G. (登録日: 2005-09-26, 公開日: 2006-05-02, 最終更新日: 2024-05-22)

主引用文献

Alana, I.,Parker, J.C.,Gault, V.A.,Flatt, P.R.,O'harte, F.P.,Malthouse, J.P.,Hewage, C.M.
NMR and alanine scan studies of glucose-dependent insulinotropic polypeptide in water.
J.Biol.Chem., 281:16370-16376, 2006

PubMed Abstract: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that stimulates the secretion of insulin after ingestion of food. GIP also promotes the synthesis of fatty acids in adipose tissue. Therefore, it is not surprising that numerous literature reports have shown that GIP is linked to diabetes and obesity-related diseases. In this study, we present the solution structure of GIP in water determined by NMR spectroscopy. The calculated structure is characterized by the presence of an alpha-helical motif between residues Ser(11) and Gln(29). The helical conformation of GIP is further supported by CD spectroscopic studies. Six GIP-(1-42)Ala(1-7) analogues were synthesized by replacing individual N-terminal residues with alanine. Alanine scan studies of these N-terminal residues showed that the GIP-(1-42)Ala(6) was the only analogue to show insulin-secreting activity similar to that of the native GIP. However, when compared with glucose, its insulinotropic ability was reduced. For the first time, these NMR and modeling results contribute to the understanding of the structural requirements for the biological activity of GIP.

PubMed: 16621806
DOI: 10.1074/jbc.M510414200

実験手法

SOLUTION NMR