1r9i

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|LIGAND= <scene name='pdbligand=CY3:2-AMINO-3-MERCAPTO-PROPIONAMIDE'>CY3</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1r9i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r9i OCA], [http://www.ebi.ac.uk/pdbsum/1r9i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1r9i RCSB]</span>
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'''NMR Solution Structure of PIIIA toxin, NMR, 20 structures'''
'''NMR Solution Structure of PIIIA toxin, NMR, 20 structures'''
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[[Category: Thomas, L.]]
[[Category: Thomas, L.]]
[[Category: Watson, M.]]
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[[Category: conotoxin]]
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[[Category: Conotoxin]]
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[[Category: cysteine knot]]
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Revision as of 04:14, 3 May 2008

Image:1r9i.jpg

Template:STRUCTURE 1r9i

NMR Solution Structure of PIIIA toxin, NMR, 20 structures


Overview

Mu-conotoxins are peptide inhibitors of voltage-sensitive sodium channels (VSSCs). Synthetic forms of mu-conotoxins PIIIA and PIIIA-(2-22) were found to inhibit tetrodotoxin (TTX)-sensitive VSSC current but had little effect on TTX-resistant VSSC current in sensory ganglion neurons. In rat brain neurons, these peptides preferentially inhibited the persistent over the transient VSSC current. Radioligand binding assays revealed that PIIIA, PIIIA-(2-22), and mu-conotoxins GIIIB discriminated among TTX-sensitive VSSCs in rat brain, that these and GIIIC discriminated among the corresponding VSSCs in human brain, and GIIIA had low affinity for neuronal VSSCs. (1)H NMR studies found that PIIIA adopts two conformations in solution due to cis/trans isomerization at hydroxyproline 8. The major trans conformation results in a three-dimensional structure that is significantly different from the previously identified conformation of mu-conotoxins GIIIA and GIIIB that selectively target TTX-sensitive muscle VSSCs. Comparison of the structures and activity of PIIIA to muscle-selective mu-conotoxins provides an insight into the structural requirements for inhibition of different TTX-sensitive sodium channels by mu-conotoxins.

About this Structure

1R9I is a Single protein structure of sequence from Conus purpurascens. Full crystallographic information is available from OCA.

Reference

Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels., Nielsen KJ, Watson M, Adams DJ, Hammarstrom AK, Gage PW, Hill JM, Craik DJ, Thomas L, Adams D, Alewood PF, Lewis RJ, J Biol Chem. 2002 Jul 26;277(30):27247-55. Epub 2002 May 2. PMID:12006587 Page seeded by OCA on Sat May 3 07:14:21 2008

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