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1ttl

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{{STRUCTURE_1ttl| PDB=1ttl | SCENE= }}
{{STRUCTURE_1ttl| PDB=1ttl | SCENE= }}
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'''Omega-conotoxin GVIA, a N-type calcium channel blocker'''
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===Omega-conotoxin GVIA, a N-type calcium channel blocker===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15166237}}
==About this Structure==
==About this Structure==
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1TTL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TTL OCA].
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1TTL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Conus_geographus Conus geographus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TTL OCA].
==Reference==
==Reference==
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[[Category: Disulfide rich]]
[[Category: Disulfide rich]]
[[Category: Four loop framework]]
[[Category: Four loop framework]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:20:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:18:43 2008''

Revision as of 03:18, 29 July 2008

Image:1ttl.png

Template:STRUCTURE 1ttl

Omega-conotoxin GVIA, a N-type calcium channel blocker

Template:ABSTRACT PUBMED 15166237

About this Structure

1TTL is a Single protein structure of sequence from Conus geographus. Full experimental 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 Tue Jul 29 06:18:43 2008

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