1tr6
From Proteopedia
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|PDB= 1tr6 |SIZE=350|CAPTION= <scene name='initialview01'>1tr6</scene> | |PDB= 1tr6 |SIZE=350|CAPTION= <scene name='initialview01'>1tr6</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=NH2:AMINO GROUP'>NH2</scene> | + | |LIGAND= <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1omc|1OMC]], [[2cco|2CCO]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tr6 OCA], [http://www.ebi.ac.uk/pdbsum/1tr6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1tr6 RCSB]</span> | ||
}} | }} | ||
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[[Category: Yasuda, T.]] | [[Category: Yasuda, T.]] | ||
[[Category: Zamponi, G W.]] | [[Category: Zamponi, G W.]] | ||
| - | [[Category: NH2]] | ||
[[Category: cysteine knot]] | [[Category: cysteine knot]] | ||
[[Category: four-loop frame work]] | [[Category: four-loop frame work]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:00:06 2008'' |
Revision as of 21:00, 30 March 2008
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| Ligands: | , | ||||||
| Related: | 1OMC, 2CCO
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR solution structure of omega-conotoxin [K10]GVIA, a cyclic cysteine knot peptide
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
1TR6 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
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