1omg
From Proteopedia
(New page: 200px<br /><applet load="1omg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1omg" /> '''NMR STUDY OF OMEGA-CONOTOXIN MVIIA'''<br /> ...) |
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| - | [[Image:1omg.jpg|left|200px]]<br /><applet load="1omg" size=" | + | [[Image:1omg.jpg|left|200px]]<br /><applet load="1omg" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1omg" /> | caption="1omg" /> | ||
'''NMR STUDY OF OMEGA-CONOTOXIN MVIIA'''<br /> | '''NMR STUDY OF OMEGA-CONOTOXIN MVIIA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The three-dimensional solution structure of omega-conotoxin MVIIA, a | + | The three-dimensional solution structure of omega-conotoxin MVIIA, a 25-mer peptide antagonist of N-type calcium channels, was determined by two-dimensional 1H NMR spectroscopy with simulated annealing calculations. A total of 13 converged structures of omega-conotoxin MVIIA were obtained on the basis of 273 experimental constraints, including 232 distance constraints obtained from nuclear Overhauser effect (NOE) connectivities, 22 torsion angle (phi, chi 1) constraints, and 19 constraints associated with hydrogen bonds and disulfide bonds. The atomic root mean square difference about the averaged coordinate positions is 0.47 +/- 0.08 A for the backbone atoms (N, C alpha, C) and 1.27 +/- 0.14 A for all heavy atoms of the entire peptide. The molecular structure of omega-conotoxin MVIIA is composed of a short triple-stranded antiparallel beta-sheet. The overall beta-sheet topology is +2x, -1, which is the same as that reported for omega-conotoxin GVIA, another N-type calcium channel blocker. The orientation of beta-stranded structure is similar to each other, suggesting that the conserved disulfide bond combination is essential for the molecular folding. We have recently determined by using alanine substitution analyses that Tyr 13 is essential for the activity of both toxins. On the basis of functional and structural analysis, it is shown that both omega-conotoxin MVIIA and GVIA retain a similar conformation to locate Tyr 13 in the appropriate position to allow binding to N-type calcium channels. These results provide a molecular basis for understanding the mechanism of calcium channel modulation through the toxin-channel interaction and insight into the discrimination of different subtypes of calcium channels. |
==About this Structure== | ==About this Structure== | ||
| - | 1OMG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Conus_magus Conus magus] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1OMG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Conus_magus Conus magus] 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=1OMG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Conus magus]] | [[Category: Conus magus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Kim, J | + | [[Category: Kim, J I.]] |
[[Category: Kobayashi, K.]] | [[Category: Kobayashi, K.]] | ||
[[Category: Kodera, Y.]] | [[Category: Kodera, Y.]] | ||
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[[Category: presynaptic neurotoxin]] | [[Category: presynaptic neurotoxin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:19:16 2008'' |
Revision as of 12:19, 21 February 2008
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NMR STUDY OF OMEGA-CONOTOXIN MVIIA
Overview
The three-dimensional solution structure of omega-conotoxin MVIIA, a 25-mer peptide antagonist of N-type calcium channels, was determined by two-dimensional 1H NMR spectroscopy with simulated annealing calculations. A total of 13 converged structures of omega-conotoxin MVIIA were obtained on the basis of 273 experimental constraints, including 232 distance constraints obtained from nuclear Overhauser effect (NOE) connectivities, 22 torsion angle (phi, chi 1) constraints, and 19 constraints associated with hydrogen bonds and disulfide bonds. The atomic root mean square difference about the averaged coordinate positions is 0.47 +/- 0.08 A for the backbone atoms (N, C alpha, C) and 1.27 +/- 0.14 A for all heavy atoms of the entire peptide. The molecular structure of omega-conotoxin MVIIA is composed of a short triple-stranded antiparallel beta-sheet. The overall beta-sheet topology is +2x, -1, which is the same as that reported for omega-conotoxin GVIA, another N-type calcium channel blocker. The orientation of beta-stranded structure is similar to each other, suggesting that the conserved disulfide bond combination is essential for the molecular folding. We have recently determined by using alanine substitution analyses that Tyr 13 is essential for the activity of both toxins. On the basis of functional and structural analysis, it is shown that both omega-conotoxin MVIIA and GVIA retain a similar conformation to locate Tyr 13 in the appropriate position to allow binding to N-type calcium channels. These results provide a molecular basis for understanding the mechanism of calcium channel modulation through the toxin-channel interaction and insight into the discrimination of different subtypes of calcium channels.
About this Structure
1OMG is a Single protein structure of sequence from Conus magus with as ligand. Full crystallographic information is available from OCA.
Reference
Three-dimensional structure in solution of the calcium channel blocker omega-conotoxin MVIIA., Kohno T, Kim JI, Kobayashi K, Kodera Y, Maeda T, Sato K, Biochemistry. 1995 Aug 15;34(32):10256-65. PMID:7640281
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