1q2j
From Proteopedia
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|PDB= 1q2j |SIZE=350|CAPTION= <scene name='initialview01'>1q2j</scene> | |PDB= 1q2j |SIZE=350|CAPTION= <scene name='initialview01'>1q2j</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1q2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q2j OCA], [http://www.ebi.ac.uk/pdbsum/1q2j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1q2j RCSB]</span> | ||
}} | }} | ||
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[[Category: mu-conotoxin]] | [[Category: mu-conotoxin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:07:54 2008'' |
Revision as of 20:07, 30 March 2008
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| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structural basis for tetrodotoxin-resistant sodium channel binding by mu-conotoxin SmIIIA
Overview
SmIIIA is a new micro-conotoxin isolated recently from Conus stercusmuscarum. Although it shares several biochemical characteristics with other micro-conotoxins (the arrangement of cysteine residues and a conserved arginine believed to interact with residues near the channel pore), it has several distinctive features, including the absence of hydroxyproline, and is the first specific antagonist of tetrodotoxin-resistant voltage-gated sodium channels to be characterized. It therefore represents a potentially useful tool to investigate the functional roles of these channels. We have determined the three-dimensional structure of SmIIIA in aqueous solution. Consistent with the absence of hydroxyprolines, SmIIIA adopts a single conformation with all peptide bonds in the trans configuration. The spatial orientations of several conserved Arg and Lys side chains, including Arg14 (using a consensus numbering system), which plays a key role in sodium channel binding, are similar to those in other micro-conotoxins but the N-terminal regions differ, reflecting the trans conformation for the peptide bond preceding residue 8 in SmIIIA, as opposed to the cis conformation in micro-conotoxins GIIIA and GIIIB. Comparison of the surfaces of SmIIIA with other micro-conotoxins suggests that the affinity of SmIIIA for TTX-resistant channels is influenced by the Trp15 side chain, which is unique to SmIIIA. Arg17, which replaces Lys in the other micro-conotoxins, may also be important. Consistent with these inferences from the structure, assays of two chimeras of SmIIIA and PIIIA in which their N- and C-terminal halves were recombined, indicated that residues in the C-terminal half of SmIIIA confer affinity for tetrodotoxin-resistant sodium channels in the cell bodies of frog sympathetic neurons. SmIIIA and the chimera possessing the C-terminal half of SmIIIA also inhibit tetrodotoxin-resistant sodium channels in the postganglionic axons of sympathetic neurons, as indicated by their inhibition of C-neuron compound action potentials that persist in the presence of tetrodotoxin.
About this Structure
1Q2J is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Structural basis for tetrodotoxin-resistant sodium channel binding by mu-conotoxin SmIIIA., Keizer DW, West PJ, Lee EF, Yoshikami D, Olivera BM, Bulaj G, Norton RS, J Biol Chem. 2003 Nov 21;278(47):46805-13. Epub 2003 Sep 10. PMID:12970353
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