1ttl
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1ttl.gif|left|200px]] | [[Image:1ttl.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1ttl", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | | | + | --> |
| - | + | {{STRUCTURE_1ttl| PDB=1ttl | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Omega-conotoxin GVIA, a N-type calcium channel blocker''' | '''Omega-conotoxin GVIA, a N-type calcium channel blocker''' | ||
| Line 33: | Line 30: | ||
[[Category: Yasuda, T.]] | [[Category: Yasuda, T.]] | ||
[[Category: Zamponi, G W.]] | [[Category: Zamponi, G W.]] | ||
| - | [[Category: | + | [[Category: Amidated c-terminal]] |
| - | [[Category: | + | [[Category: Disulfide rich]] |
| - | [[Category: | + | [[Category: Four loop framework]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:20:49 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:20, 3 May 2008
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. 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 Sat May 3 10:20:49 2008
