2b4n
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2b4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b4n OCA], [http://www.ebi.ac.uk/pdbsum/2b4n PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2b4n RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Pituitary ACTH-secreting adenoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139360 139360]], Ventricular tachycardia, idiopathic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139360 139360]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: obesity]] | [[Category: obesity]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:01:22 2008'' |
Revision as of 23:01, 30 March 2008
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Solution Structure of Glucose-Dependent Insulinotropic Polypeptide
Overview
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.
About this Structure
2B4N is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
NMR and alanine scan studies of glucose-dependent insulinotropic polypeptide in water., Alana I, Parker JC, Gault VA, Flatt PR, O'Harte FP, Malthouse JP, Hewage CM, J Biol Chem. 2006 Jun 16;281(24):16370-6. Epub 2006 Apr 18. PMID:16621806
Page seeded by OCA on Mon Mar 31 02:01:22 2008
Categories: Homo sapiens | Single protein | Alana, I. | Harte, F P.M O. | Hewage, C M. | Malthouse, J P.G. | Diabetes | Gip | Helix | Molecular modelling | Nmr | Obesity
