1ttk
From Proteopedia
(New page: 200px<br /><applet load="1ttk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ttk" /> '''NMR solution structure of omega-conotoxin MV...) |
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| - | [[Image:1ttk.gif|left|200px]]<br /><applet load="1ttk" size=" | + | [[Image:1ttk.gif|left|200px]]<br /><applet load="1ttk" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ttk" /> | caption="1ttk" /> | ||
'''NMR solution structure of omega-conotoxin MVIIA, a N-type calcium channel blocker'''<br /> | '''NMR solution structure of omega-conotoxin MVIIA, a N-type calcium channel blocker'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Neurotransmitter release from preganglionic parasympathetic neurons is | + | Neurotransmitter release from preganglionic parasympathetic neurons is resistant to inhibition by selective antagonists of L-, N-, P/Q-, R-, and T-type calcium channels. In this study, the effects of different omega-conotoxins from genus Conus were investigated on current flow-through cloned voltage-sensitive calcium channels expressed in Xenopus oocytes and nerve-evoked transmitter release from the intact preganglionic cholinergic nerves innervating the rat submandibular ganglia. Our results indicate that omega-conotoxin CVID from Conus catus inhibits a pharmacologically distinct voltage-sensitive calcium channel involved in neurotransmitter release, whereas omega-conotoxin MVIIA had no effect. omega-Conotoxin CVID and MVIIA inhibited depolarization-activated Ba(2+) currents recorded from oocytes expressing N-type but not L- or R-type calcium channels. High affinity inhibition of the CVID-sensitive calcium channel was enhanced when position 10 of the omega-conotoxin was occupied by the smaller residue lysine as found in CVID instead of an arginine as found in MVIIA. Given that relatively small differences in the sequence of the N-type calcium channel alpha(1B) subunit can influence omega-conotoxin access (Feng, Z. P., Hamid, J., Doering, C., Bosey, G. M., Snutch, T. P., and Zamponi, G. W. (2001) J. Biol. Chem. 276, 15728-15735), it is likely that the calcium channel in preganglionic nerve terminals targeted by CVID is a N-type (Ca(v)2.2) calcium channel variant. |
==About this Structure== | ==About this Structure== | ||
| - | 1TTK 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:// | + | 1TTK 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=1TTK OCA]. |
==Reference== | ==Reference== | ||
Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-sensitive calcium channel associated with transmitter release from preganglionic nerve terminals., Adams DJ, Smith AB, Schroeder CI, Yasuda T, Lewis RJ, J Biol Chem. 2003 Feb 7;278(6):4057-62. Epub 2002 Nov 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12441339 12441339] | Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-sensitive calcium channel associated with transmitter release from preganglionic nerve terminals., Adams DJ, Smith AB, Schroeder CI, Yasuda T, Lewis RJ, J Biol Chem. 2003 Feb 7;278(6):4057-62. Epub 2002 Nov 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12441339 12441339] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Adams, D | + | [[Category: Adams, D J.]] |
| - | [[Category: Lewis, R | + | [[Category: Lewis, R J.]] |
| - | [[Category: Schroeder, C | + | [[Category: Schroeder, C I.]] |
| - | [[Category: Smith, A | + | [[Category: Smith, A B.]] |
[[Category: Yasuda, T.]] | [[Category: Yasuda, T.]] | ||
[[Category: NH2]] | [[Category: NH2]] | ||
| Line 22: | Line 22: | ||
[[Category: four loop frame work]] | [[Category: four loop frame work]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:17:12 2008'' |
Revision as of 13:17, 21 February 2008
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NMR solution structure of omega-conotoxin MVIIA, a N-type calcium channel blocker
Overview
Neurotransmitter release from preganglionic parasympathetic neurons is resistant to inhibition by selective antagonists of L-, N-, P/Q-, R-, and T-type calcium channels. In this study, the effects of different omega-conotoxins from genus Conus were investigated on current flow-through cloned voltage-sensitive calcium channels expressed in Xenopus oocytes and nerve-evoked transmitter release from the intact preganglionic cholinergic nerves innervating the rat submandibular ganglia. Our results indicate that omega-conotoxin CVID from Conus catus inhibits a pharmacologically distinct voltage-sensitive calcium channel involved in neurotransmitter release, whereas omega-conotoxin MVIIA had no effect. omega-Conotoxin CVID and MVIIA inhibited depolarization-activated Ba(2+) currents recorded from oocytes expressing N-type but not L- or R-type calcium channels. High affinity inhibition of the CVID-sensitive calcium channel was enhanced when position 10 of the omega-conotoxin was occupied by the smaller residue lysine as found in CVID instead of an arginine as found in MVIIA. Given that relatively small differences in the sequence of the N-type calcium channel alpha(1B) subunit can influence omega-conotoxin access (Feng, Z. P., Hamid, J., Doering, C., Bosey, G. M., Snutch, T. P., and Zamponi, G. W. (2001) J. Biol. Chem. 276, 15728-15735), it is likely that the calcium channel in preganglionic nerve terminals targeted by CVID is a N-type (Ca(v)2.2) calcium channel variant.
About this Structure
1TTK is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-sensitive calcium channel associated with transmitter release from preganglionic nerve terminals., Adams DJ, Smith AB, Schroeder CI, Yasuda T, Lewis RJ, J Biol Chem. 2003 Feb 7;278(6):4057-62. Epub 2002 Nov 18. PMID:12441339
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