1nau
From Proteopedia
(New page: 200px<br /> <applet load="1nau" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nau" /> '''NMR Solution Structure of the Glucagon Anta...) |
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'''NMR Solution Structure of the Glucagon Antagonist [desHis1, desPhe6, Glu9]Glucagon Amide in the Presence of Perdeuterated Dodecylphosphocholine Micelles'''<br /> | '''NMR Solution Structure of the Glucagon Antagonist [desHis1, desPhe6, Glu9]Glucagon Amide in the Presence of Perdeuterated Dodecylphosphocholine Micelles'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Glucagon, a 29-residue peptide hormone, plays an important role in glucose | + | Glucagon, a 29-residue peptide hormone, plays an important role in glucose homeostasis and in diabetes mellitus. Several glucagon antagonists and agonists have been developed, but limited structural information is available to clarify the basis of their biological activity. The solution structure of the potent glucagon antagonist, [desHis1, desPhe6, Glu9]glucagon amide, was determined by homonuclear 2D NMR spectroscopy at pH 6.0 and 37 degrees C in perdeuterated dodecylphosphocholine micelles. The overall backbone root-mean-square deviation (rmsd) for the structured portion (residues 7-29, glucagon numbering) of the micelle-bound 27-residue peptide is 1.36 A for the 15 lowest-energy structures, after restrained molecular dynamics simulation. The structure consists of four regions (segment backbone rmsd in A): an unstructured N-terminal segment between residues 2 and 5 (1.68), an irregular helix between residues 7 and 14 (0.79), a hinge region between residues 15 and 18 (0.54), and a well-defined alpha-helix between residues 19 and 29 (0.33). The two helices form an L-shaped structure with an angle of about 90 degrees between the helix axes. There is an extended hydrophobic cluster, which runs along the inner surface of the L-structure and incorporates the side chains of the hydrophobic residues of each of the amphipathic helices. The outer surface contains the hydrophilic side chains, with two salt bridges (D15-R18 and R17-D21) implied from close approach of the charged groups. This result is the first clear indication of an overall tertiary fold for a glucagon analogue in the micelle-bound state. The relationship of the two helical structural elements may have important implications for the biological activity of the glucagon antagonist. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1NAU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1NAU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NAU OCA]. |
==Reference== | ==Reference== | ||
NMR solution structure of the glucagon antagonist [desHis1, desPhe6, Glu9]glucagon amide in the presence of perdeuterated dodecylphosphocholine micelles., Ying J, Ahn JM, Jacobsen NE, Brown MF, Hruby VJ, Biochemistry. 2003 Mar 18;42(10):2825-35. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12627948 12627948] | NMR solution structure of the glucagon antagonist [desHis1, desPhe6, Glu9]glucagon amide in the presence of perdeuterated dodecylphosphocholine micelles., Ying J, Ahn JM, Jacobsen NE, Brown MF, Hruby VJ, Biochemistry. 2003 Mar 18;42(10):2825-35. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12627948 12627948] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Ahn, J | + | [[Category: Ahn, J M.]] |
| - | [[Category: Brown, M | + | [[Category: Brown, M F.]] |
| - | [[Category: Hruby, V | + | [[Category: Hruby, V J.]] |
| - | [[Category: Jacobsen, N | + | [[Category: Jacobsen, N E.]] |
[[Category: Ying, J.]] | [[Category: Ying, J.]] | ||
[[Category: NH2]] | [[Category: NH2]] | ||
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[[Category: turn]] | [[Category: turn]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:04:04 2008'' |
Revision as of 12:04, 21 February 2008
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NMR Solution Structure of the Glucagon Antagonist [desHis1, desPhe6, Glu9]Glucagon Amide in the Presence of Perdeuterated Dodecylphosphocholine Micelles
Contents |
Overview
Glucagon, a 29-residue peptide hormone, plays an important role in glucose homeostasis and in diabetes mellitus. Several glucagon antagonists and agonists have been developed, but limited structural information is available to clarify the basis of their biological activity. The solution structure of the potent glucagon antagonist, [desHis1, desPhe6, Glu9]glucagon amide, was determined by homonuclear 2D NMR spectroscopy at pH 6.0 and 37 degrees C in perdeuterated dodecylphosphocholine micelles. The overall backbone root-mean-square deviation (rmsd) for the structured portion (residues 7-29, glucagon numbering) of the micelle-bound 27-residue peptide is 1.36 A for the 15 lowest-energy structures, after restrained molecular dynamics simulation. The structure consists of four regions (segment backbone rmsd in A): an unstructured N-terminal segment between residues 2 and 5 (1.68), an irregular helix between residues 7 and 14 (0.79), a hinge region between residues 15 and 18 (0.54), and a well-defined alpha-helix between residues 19 and 29 (0.33). The two helices form an L-shaped structure with an angle of about 90 degrees between the helix axes. There is an extended hydrophobic cluster, which runs along the inner surface of the L-structure and incorporates the side chains of the hydrophobic residues of each of the amphipathic helices. The outer surface contains the hydrophilic side chains, with two salt bridges (D15-R18 and R17-D21) implied from close approach of the charged groups. This result is the first clear indication of an overall tertiary fold for a glucagon analogue in the micelle-bound state. The relationship of the two helical structural elements may have important implications for the biological activity of the glucagon antagonist.
Disease
Known disease associated with this structure: Hyperproglucagonemia OMIM:[138030]
About this Structure
1NAU is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
NMR solution structure of the glucagon antagonist [desHis1, desPhe6, Glu9]glucagon amide in the presence of perdeuterated dodecylphosphocholine micelles., Ying J, Ahn JM, Jacobsen NE, Brown MF, Hruby VJ, Biochemistry. 2003 Mar 18;42(10):2825-35. PMID:12627948
Page seeded by OCA on Thu Feb 21 14:04:04 2008
Categories: Single protein | Ahn, J M. | Brown, M F. | Hruby, V J. | Jacobsen, N E. | Ying, J. | NH2 | Helix | Turn
