1t0c
From Proteopedia
(New page: 200px<br /> <applet load="1t0c" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t0c" /> '''Solution Structure of Human Proinsulin C-Pe...) |
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'''Solution Structure of Human Proinsulin C-Peptide'''<br /> | '''Solution Structure of Human Proinsulin C-Peptide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The C-peptide of proinsulin is important for the biosynthesis of insulin, but has been considered for a long time to be biologically inert. Recent | + | The C-peptide of proinsulin is important for the biosynthesis of insulin, but has been considered for a long time to be biologically inert. Recent studies in diabetic patients have stimulated a new debate about its possible regulatory role, suggesting that it is a hormonally active peptide. We describe structural studies of the C-peptide using 2D NMR spectroscopy. In aqueous solution, the NOE patterns and chemical shifts indicate that the ensemble is a nonrandom structure and contains substructures with defined local conformations. These are more clearly visible in 50% H2O/50% 2,2,2-trifluoroethanol. The N-terminal region (residues 2-5) forms a type I beta-turn, whereas the C-terminal region (residues 27-31) presents the most well-defined structure of the whole molecule including a type III'beta-turn. The C-terminal pentapeptide (EGSLQ) has been suggested to be responsible for chiral interactions with an as yet uncharacterized, probably a G-protein-coupled, receptor. The three central regions of the molecule (residues 9-12, 15-18 and 22-25) show tendencies to form beta-bends. We propose that the structure described here for the C-terminal pentapeptide is consistent with the previously postulated CA knuckle, believed to represent the active site of the C-peptide of human proinsulin. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1T0C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1T0C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T0C OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Garratt, R | + | [[Category: Garratt, R C.]] |
| - | [[Category: Kalbitzer, H | + | [[Category: Kalbitzer, H R.]] |
| - | [[Category: Munte, C | + | [[Category: Munte, C E.]] |
[[Category: Vilela, L.]] | [[Category: Vilela, L.]] | ||
[[Category: bend]] | [[Category: bend]] | ||
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[[Category: type iii' beta-turn]] | [[Category: type iii' beta-turn]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:08:29 2008'' |
Revision as of 13:08, 21 February 2008
|
Solution Structure of Human Proinsulin C-Peptide
Contents |
Overview
The C-peptide of proinsulin is important for the biosynthesis of insulin, but has been considered for a long time to be biologically inert. Recent studies in diabetic patients have stimulated a new debate about its possible regulatory role, suggesting that it is a hormonally active peptide. We describe structural studies of the C-peptide using 2D NMR spectroscopy. In aqueous solution, the NOE patterns and chemical shifts indicate that the ensemble is a nonrandom structure and contains substructures with defined local conformations. These are more clearly visible in 50% H2O/50% 2,2,2-trifluoroethanol. The N-terminal region (residues 2-5) forms a type I beta-turn, whereas the C-terminal region (residues 27-31) presents the most well-defined structure of the whole molecule including a type III'beta-turn. The C-terminal pentapeptide (EGSLQ) has been suggested to be responsible for chiral interactions with an as yet uncharacterized, probably a G-protein-coupled, receptor. The three central regions of the molecule (residues 9-12, 15-18 and 22-25) show tendencies to form beta-bends. We propose that the structure described here for the C-terminal pentapeptide is consistent with the previously postulated CA knuckle, believed to represent the active site of the C-peptide of human proinsulin.
Disease
Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[176730], Hyperproinsulinemia, familial OMIM:[176730], MODY, one form OMIM:[176730]
About this Structure
1T0C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure of human proinsulin C-peptide., Munte CE, Vilela L, Kalbitzer HR, Garratt RC, FEBS J. 2005 Aug;272(16):4284-93. PMID:16098208
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