1q2j
From Proteopedia
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| - | [[Image:1q2j.png|left|200px]] | ||
| - | + | ==Structural basis for tetrodotoxin-resistant sodium channel binding by mu-conotoxin SmIIIA== | |
| + | <StructureSection load='1q2j' size='340' side='right'caption='[[1q2j]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1q2j]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_stercusmuscarum Conus stercusmuscarum]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q2J FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q2j OCA], [https://pdbe.org/1q2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q2j RCSB], [https://www.ebi.ac.uk/pdbsum/1q2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q2j ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CM3A_CONSE CM3A_CONSE] Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin blocks rNav1.5/SCN5A (IC(50) is 1.3 uM), rNav1.6/SCN8A (IC(50) is 160 nM), rNav1.7/SCN9A (IC(50) is 1.3 uM), rNav1.1/SCN1A (K(d) is 3.8 nM), rNav1.2/SCN2A (K(d) is 1.3 nM), rNav1.4/SCN4A (K(d) is 0.22 nM), rNav1.6/SCN8A (K(d) is 69 nM), and rNav1.7/SCN9A (K(d) is 260 nM). This toxin is very potent but weakly discriminating among sodium channels. The block of these channels is modified when beta-subunits are coexpressed with alpha subunits. Hence, blocks of channels containing beta-1 and beta-3 subunits are more potent (compared to channels without beta subunits), whereas blocks of channels containing beta-2 and beta-4 subunits are less potent (compared to channels without beta subunits).<ref>PMID:12484778</ref> <ref>PMID:21652775</ref> <ref>PMID:22229737</ref> <ref>PMID:23146020</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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<ref>PMID:12970353</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | == | + | <div class="pdbe-citations 1q2j" style="background-color:#fffaf0;"></div> |
| - | [[ | + | == References == |
| - | [[Category: Bulaj | + | <references/> |
| - | [[Category: Keizer | + | __TOC__ |
| - | [[Category: Lee | + | </StructureSection> |
| - | [[Category: Norton | + | [[Category: Conus stercusmuscarum]] |
| - | [[Category: Olivera | + | [[Category: Large Structures]] |
| - | [[Category: West | + | [[Category: Bulaj G]] |
| - | [[Category: Yoshikami | + | [[Category: Keizer DW]] |
| - | + | [[Category: Lee EF]] | |
| - | + | [[Category: Norton RS]] | |
| + | [[Category: Olivera BM]] | ||
| + | [[Category: West PJ]] | ||
| + | [[Category: Yoshikami D]] | ||
Current revision
Structural basis for tetrodotoxin-resistant sodium channel binding by mu-conotoxin SmIIIA
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