Linked Life Data

21539943

Source:http://linkedlifedata.com/resource/pubmed/id/21539943

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-5-27
pubmed:abstractText
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 ?-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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-3002
pubmed:author
pubmed:copyrightInfo
2011 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:volume
1814
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
882-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21539943-Alanine, pubmed-meshheading:21539943-Amino Acid Sequence, pubmed-meshheading:21539943-Animals, pubmed-meshheading:21539943-Cell Line, Tumor, pubmed-meshheading:21539943-Dose-Response Relationship, Drug, pubmed-meshheading:21539943-Gastric Inhibitory Polypeptide, pubmed-meshheading:21539943-Glucose, pubmed-meshheading:21539943-Humans, pubmed-meshheading:21539943-Hydrogen Bonding, pubmed-meshheading:21539943-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:21539943-Insulin, pubmed-meshheading:21539943-Islets of Langerhans, pubmed-meshheading:21539943-Models, Molecular, pubmed-meshheading:21539943-Molecular Sequence Data, pubmed-meshheading:21539943-Peptide Fragments, pubmed-meshheading:21539943-Protein Binding, pubmed-meshheading:21539943-Protein Conformation, pubmed-meshheading:21539943-Protein Structure, Secondary, pubmed-meshheading:21539943-Protein Structure, Tertiary, pubmed-meshheading:21539943-Receptors, Gastrointestinal Hormone
pubmed:year
2011
pubmed:articleTitle
Conformational, receptor interaction and alanine scan studies of glucose-dependent insulinotropic polypeptide.
pubmed:affiliation
School of Biomolecular and Biomedical Science, Centre for Synthesis and Chemical Biology, SEC Strategic Research Cluster, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't