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1ttk

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(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="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:1ttk.gif|left|200px]]<br /><applet load="1ttk" size="350" color="white" frame="true" align="right" spinBox="true"
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'''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==
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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.
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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==
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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TTK OCA].
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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]]
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[[Category: Adams, D.J.]]
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[[Category: Adams, D J.]]
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[[Category: Lewis, R.J.]]
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[[Category: Lewis, R J.]]
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[[Category: Schroeder, C.I.]]
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[[Category: Schroeder, C I.]]
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[[Category: Smith, A.B.]]
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[[Category: Smith, A B.]]
[[Category: Yasuda, T.]]
[[Category: Yasuda, T.]]
[[Category: NH2]]
[[Category: NH2]]
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[[Category: four loop frame work]]
[[Category: four loop frame work]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:34:56 2007''
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''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


1ttk

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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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