2obu: Difference between revisions
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New page: left|200px<br /> <applet load="2obu" size="450" color="white" frame="true" align="right" spinBox="true" caption="2obu" /> '''Solution structure of GIP in TFE/water'''<b... |
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[[Image:2obu.gif|left|200px]]<br /> | [[Image:2obu.gif|left|200px]]<br /><applet load="2obu" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2obu" size=" | |||
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'''Solution structure of GIP in TFE/water'''<br /> | '''Solution structure of GIP in TFE/water'''<br /> | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
2OBU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | 2OBU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OBU OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: gip; nmr; molecular modelling; helix; diabetes; obesity]] | [[Category: gip; nmr; molecular modelling; helix; diabetes; obesity]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:01:11 2008'' | ||
