NMR structure of the glucose-dependent insulinotropic polypeptide fragment, GIP(1-30)amide

Biochem Biophys Res Commun. 2004 Dec 3;325(1):281-6. doi: 10.1016/j.bbrc.2004.10.033.

Abstract

Glucose-dependent insulinotropic polypeptide is an incretin hormone that stimulates insulin secretion and reduces postprandial glycaemic excursions. The glucose-dependent action of GIP on pancreatic beta-cells has attracted attention towards its exploitation as a potential drug for type 2 diabetes. Use of NMR or X-ray crystallography is vital to determine the three-dimensional structure of the peptide. Therefore, to understand the basic structural requirements for the biological activity of GIP, the solution structure of the major biologically active fragment, GIP(1-30)amide, was investigated by proton NMR spectroscopy and molecular modelling. The structure is characterised by a full length alpha-helical conformation between residues F(6) and A(28). This structural information could play an important role in the design of therapeutic agents based upon GIP receptor agonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Gastric Inhibitory Polypeptide / chemistry*
  • Gastric Inhibitory Polypeptide / metabolism
  • Humans
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Protein Structure, Tertiary*

Substances

  • Peptide Fragments
  • Gastric Inhibitory Polypeptide

Associated data

  • PDB/1T5Q