1eit
From Proteopedia
(New page: 200px<br /><applet load="1eit" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eit" /> '''NMR STUDY OF MU-AGATOXIN'''<br /> ==Overvie...) |
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| - | [[Image:1eit.jpg|left|200px]]<br /><applet load="1eit" size=" | + | [[Image:1eit.jpg|left|200px]]<br /><applet load="1eit" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''NMR STUDY OF MU-AGATOXIN'''<br /> | '''NMR STUDY OF MU-AGATOXIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We report the solution structure of mu-agatoxin-I (mu-Aga-I) and model | + | We report the solution structure of mu-agatoxin-I (mu-Aga-I) and model structures of the closely related mu-agatoxin-IV (mu-Aga-IV) which were isolated from venom of the American funnel web spider, Agelenopsis aperta. These toxins, which modify the kinetics of neuronal voltage-activated sodium channels in insects, are C-terminally amidated peptides composed to 36 amino acids, including four internal disulfide bonds. The structure of mu-Aga-I was determined by NMR and distance geometry/molecular dynamics calculations. Structural calculations were carried out using 256 interresidue NOE-derived distance restraints and 25 angle restraints obtained from vicinal coupling constants. The peptide contains eight cysteines involved in disulfide bonds, the pairings of which were uncertain and had to be determined from preliminary structure calculations. The toxin has an average rmsd of 0.89 A for the backbone atoms among 38 converged conformers. The structure consists of a well-defined triple-stranded beta-sheet involving residues 7-9, 20-24, and 30-34 and four tight turns. A homologous peptide, mu-Aga-IV, exhibited two distinct and equally populated conformations in solution, which complicated spectral analysis. Analysis of sequential NOE's confirmed that the conformers arose from cis and trans peptide bonds involving a proline at position 15. Models were developed for both conformers based on the mu-Aga-I structure. Our structural data show that the mu-agatoxins, although specific modifiers of sodium channels, share common secondary and tertiary structural motifs with phylogenetically diverse peptide toxins targeting a variety of channel types. The mu-agatoxins add voltage-sensitive sodium channel activity to a growing list of neurotoxic effects elicited by peptide toxins which share the same global fold yet differ in their animal origin and ion channel selectivity. |
==About this Structure== | ==About this Structure== | ||
| - | 1EIT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Agelenopsis_aperta Agelenopsis aperta] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1EIT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Agelenopsis_aperta Agelenopsis aperta] 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=1EIT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Agelenopsis aperta]] | [[Category: Agelenopsis aperta]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Omecinsky, D | + | [[Category: Omecinsky, D O.]] |
| - | [[Category: Reily, M | + | [[Category: Reily, M D.]] |
[[Category: NH2]] | [[Category: NH2]] | ||
[[Category: excitatory insect toxin]] | [[Category: excitatory insect toxin]] | ||
[[Category: neurotoxin]] | [[Category: neurotoxin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:28:14 2008'' |
Revision as of 10:28, 21 February 2008
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NMR STUDY OF MU-AGATOXIN
Overview
We report the solution structure of mu-agatoxin-I (mu-Aga-I) and model structures of the closely related mu-agatoxin-IV (mu-Aga-IV) which were isolated from venom of the American funnel web spider, Agelenopsis aperta. These toxins, which modify the kinetics of neuronal voltage-activated sodium channels in insects, are C-terminally amidated peptides composed to 36 amino acids, including four internal disulfide bonds. The structure of mu-Aga-I was determined by NMR and distance geometry/molecular dynamics calculations. Structural calculations were carried out using 256 interresidue NOE-derived distance restraints and 25 angle restraints obtained from vicinal coupling constants. The peptide contains eight cysteines involved in disulfide bonds, the pairings of which were uncertain and had to be determined from preliminary structure calculations. The toxin has an average rmsd of 0.89 A for the backbone atoms among 38 converged conformers. The structure consists of a well-defined triple-stranded beta-sheet involving residues 7-9, 20-24, and 30-34 and four tight turns. A homologous peptide, mu-Aga-IV, exhibited two distinct and equally populated conformations in solution, which complicated spectral analysis. Analysis of sequential NOE's confirmed that the conformers arose from cis and trans peptide bonds involving a proline at position 15. Models were developed for both conformers based on the mu-Aga-I structure. Our structural data show that the mu-agatoxins, although specific modifiers of sodium channels, share common secondary and tertiary structural motifs with phylogenetically diverse peptide toxins targeting a variety of channel types. The mu-agatoxins add voltage-sensitive sodium channel activity to a growing list of neurotoxic effects elicited by peptide toxins which share the same global fold yet differ in their animal origin and ion channel selectivity.
About this Structure
1EIT is a Single protein structure of sequence from Agelenopsis aperta with as ligand. Full crystallographic information is available from OCA.
Reference
Three-dimensional structure analysis of mu-agatoxins: further evidence for common motifs among neurotoxins with diverse ion channel specificities., Omecinsky DO, Holub KE, Adams ME, Reily MD, Biochemistry. 1996 Mar 5;35(9):2836-44. PMID:8608119
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