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1tt3

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Revision as of 01:27, 21 November 2007


1tt3

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NMR soulution structure of omega-conotoxin [K10]MVIIA

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

1TT3 is a Single protein structure of sequence from [1] with NH2 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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