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1ttl
From Proteopedia
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(New page: 200px<br /><applet load="1ttl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ttl" /> '''Omega-conotoxin GVIA, a N-type calcium chann...)
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Revision as of 01:27, 21 November 2007
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Omega-conotoxin GVIA, a N-type calcium channel blocker
Overview
The omega-conotoxins from fish-hunting cone snails are potent inhibitors, of voltage-gated calcium channels. The omega-conotoxins MVIIA and CVID are, selective N-type calcium channel inhibitors with potential in the, treatment of chronic pain. The beta and alpha(2)delta-1 auxiliary subunits, influence the expression and characteristics of the alpha(1B) subunit of, N-type channels and are differentially regulated in disease states, including pain. In this study, we examined the influence of these, auxiliary subunits on the ability of the omega-conotoxins GVIA, MVIIA, CVID and analogues to inhibit peripheral and central forms of the rat, N-type channels. Although the beta3 subunit had little influence on the, on- and off-rates of omega-conotoxins, coexpression of alpha(2)delta with, alpha(1B) significantly reduced on-rates and equilibrium inhibition at, both the central and peripheral isoforms of the N-type channels. The, alpha(2)delta also enhanced the selectivity of MVIIA, but not CVID, for, the central isoform. Similar but less pronounced trends were also observed, for N-type channels expressed in human embryonic kidney cells. The, influence of alpha(2)delta was not affected by oocyte deglycosylation. The, extent of recovery from the omega-conotoxin block was least for GVIA, intermediate for MVIIA, and almost complete for CVID. Application of a, hyperpolarizing holding potential (-120 mV) did not significantly enhance, the extent of CVID recovery. Interestingly, [R10K]MVIIA and [O10K]GVIA had, greater recovery from the block, whereas [K10R]CVID had reduced recovery, from the block, indicating that position 10 had an important influence on, the extent of omega-conotoxin reversibility. Recovery from CVID block was, reduced in the presence of alpha(2)delta in human embryonic kidney cells, and in oocytes expressing alpha(1B-b). These results may have implications, for the antinociceptive properties of omega-conotoxins, given that the, alpha(2)delta subunit is up-regulated in certain pain states.
About this Structure
1TTL is a Single protein structure of sequence from Conus geographus with NH2 as ligand. Full crystallographic information is available from OCA.
Reference
The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels., Mould J, Yasuda T, Schroeder CI, Beedle AM, Doering CJ, Zamponi GW, Adams DJ, Lewis RJ, J Biol Chem. 2004 Aug 13;279(33):34705-14. Epub 2004 May 27. PMID:15166237
Page seeded by OCA on Wed Nov 21 03:35:00 2007
