2l71

NMR solution structure of GIP in Bicellular media

spinqualitylabelsall models 2l71, 15 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2l71 is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 1t5q, 2b4n, 2obu, 2l70 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [GIP_HUMAN] Potent stimulator of insulin secretion and relatively poor inhibitor of gastric acid secretion. Publication Abstract from PubMed Glucose-dependent insulinotropic polypeptide (GIP) is an insulinotropic incretin hormone that stimulates insulin secretion during a meal. GIP has glucose lowering abilities and hence is considered as a potential target molecule for type 2 diabetes therapy. In this article, we present the solution structure of GIP in membrane-mimicking environments by proton NMR spectroscopy and molecular modelling. GIP adopts an alpha-helical conformation between residues Phe(6)-Gly(31) and Ala(13)-Gln(29) for micellar and bicellar media, respectively. Previously we examined the effect of N-terminal Ala substitution in GIP, but here eight GIP analogues were synthesised by replacing individual residues within the central 8-18 region with alanine. These studies showed relatively minor changes in biological activity as assessed by insulin releasing potency. However, at higher concentration, GIP(Ala(16)), and GIP(Ala(18)) showed insulin secreting activity higher than the native GIP (P<0.01 to P<0.001) in cultured pancreatic BRIN-BD11 cells. Receptor interaction studies of the native GIP with the extracellular domain of its receptor were performed by using two different docking algorithms. At the optimised docking conformation, the complex was stabilised by the presence of hydrophobic interactions and intermolecular hydrogen bonding. Further, we have identified some potentially important additional C-terminal interactions of GIP with its N-terminal extracellular receptor domain. Conformational, receptor interaction and alanine scan studies of glucose-dependent insulinotropic polypeptide.,Venneti KC, Malthouse JP, O'Harte FP, Hewage CM Biochim Biophys Acta. 2011 Jul;1814(7):882-8. Epub 2011 Apr 27. PMID:21539943 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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