NMR and alanine scan studies of glucose-dependent insulinotropic polypeptide in water

The Journal of Biological Chemistry
Iñigo AlañaChandralal M Hewage

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.

References

Feb 1, 1996·Journal of Molecular Graphics·R KoradiK Wüthrich
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Nov 21, 1997·Journal of Molecular Biology·P GüntertK Wüthrich
Dec 12, 2001·Bioorganic & Medicinal Chemistry·Niels H AndersenKathryn S Prickett
Jun 18, 2002·Nature Medicine·Kazumasa MiyawakiYutaka Seino
Jul 10, 2002·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Jens J Holst
Oct 9, 2002·Current Protein & Peptide Science·S M Kelly, N C Price
Aug 11, 2004·Life Sciences·Simon A HinkeChristopher H S McIntosh
Nov 4, 2004·Biochemical and Biophysical Research Communications·Iñigo AlañaFinbarr P M O'Harte
Jun 1, 2005·The Journal of Pharmacology and Experimental Therapeutics·Nigel IrwinPeter R Flatt
Jul 20, 2005·Biochimica Et Biophysica Acta·Sharon M KellyNicholas C Price

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Citations

Apr 23, 2013·Alzheimer's Research & Therapy·Emilie Faivre, Christian Hölscher
Aug 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Christoph ParthierMilton T Stubbs
May 5, 2011·Biochimica Et Biophysica Acta·Kalyana C VennetiChandralal M Hewage
Jun 18, 2010·Peptides·Anusha P SubasinghageChandralal M Hewage
May 19, 2009·Trends in Biochemical Sciences·Christoph ParthierMilton T Stubbs
Apr 18, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Alpeshkumar K MaldeEvans C Coutinho
Jul 8, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Sonali H TikheleEvans C Coutinho
Dec 28, 2010·Biochemical and Biophysical Research Communications·Barry D KerrVictor A Gault
Jul 13, 2007·Molecular Nutrition & Food Research·Inke NitzFrank Döring
Aug 20, 2018·The Journal of Endocrinology·Guillaume MabilleauDaniel Chappard
Jan 8, 2013·ChemMedChem·Chandralal M Hewage, Kalyana C Venneti
Jun 27, 2017·Biomedicine Hub·Ruxana T SadikotIsrael Rubinstein
Mar 18, 2021·PLoS Computational Biology·Alican Gulsevin, Jens Meiler
May 16, 2014·Biochemistry·Petra RovóAndrás Perczel
Sep 28, 2021·Journal of Peptide Science : an Official Publication of the European Peptide Society·Patrick B Timmons, Chandralal M Hewage

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