2OBU
Solution structure of GIP in TFE/water
Summary for 2OBU
| Entry DOI | 10.2210/pdb2obu/pdb |
| NMR Information | BMRB: 6681 |
| Descriptor | Gastric inhibitory polypeptide (1 entity in total) |
| Functional Keywords | gip; nmr; molecular modelling; helix; diabetes; obesity, hormone-growth factor complex, hormone/growth factor |
| Cellular location | Secreted: P09681 |
| Total number of polymer chains | 1 |
| Total formula weight | 4990.59 |
| Authors | Alana, I.,Malthouse, J.P.G.,O'Harte, F.P.M.,Hewage, C.M. (deposition date: 2006-12-20, release date: 2007-06-05, Last modification date: 2023-12-27) |
| Primary citation | Alana, I.,Malthouse, J.P.G.,O'harte, F.P.M.,Hewage, C.M. The bioactive conformation of glucose-dependent insulinotropic polypeptide by NMR and CD spectroscopy Proteins, 68:92-99, 2007 Cited by PubMed Abstract: Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal incretin hormone, which modulates physiological insulin secretion. Because of its glucose-sensitive insulinotropic activity, there has been a considerable interest in utilizing the hormone as a potential treatment for type 2 diabetes. Structural parameters obtained from NMR spectroscopy combined with molecular modeling techniques play a vital role in the design of new therapeutic drugs. Therefore, to understand the structural requirements for the biological activity of GIP, the solution structure of GIP was investigated by circular dichroism (CD) followed by proton nuclear magnetic resonance (NMR) spectroscopy. CD studies showed an increase in the helical character of the peptide with increasing concentration of trifluoroethanol (TFE) up to 50%. Therefore, the solution structure of GIP in 50% TFE was determined. It was found that there was an alpha-helix between residues 6 and 29, which tends to extend further up to residue 36. The implications of the C-terminal extended helical segment in the inhibitory properties of GIP on gastric acid secretion are discussed. It is shown that the adoption by GIP of an alpha-helical secondary structure is a requirement for its biological activity. Knowledge of the solution structure of GIP will help in the understanding of how the peptide interacts with its receptor and aids in the design of new therapeutic agents useful for the treatment of diabetes. PubMed: 17393464DOI: 10.1002/prot.21372 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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