2B4N
Solution Structure of Glucose-Dependent Insulinotropic Polypeptide
Summary for 2B4N
| Entry DOI | 10.2210/pdb2b4n/pdb |
| Descriptor | Gastric inhibitory polypeptide (1 entity in total) |
| Functional Keywords | gip, molecular modelling, helix, diabetes, obesity, hormone-growth factor complex, hormone/growth factor |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted: P09681 |
| Total number of polymer chains | 1 |
| Total formula weight | 4990.59 |
| Authors | Alana, I.,Hewage, C.M.,O'Harte, F.P.M.,Malthouse, J.P.G. (deposition date: 2005-09-26, release date: 2006-05-02, Last modification date: 2024-05-22) |
| Primary citation | 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 Cited by 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: 16621806DOI: 10.1074/jbc.M510414200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
