| http://purl.uniprot.org/citations/18522941 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18522941 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18522941 | http://www.w3.org/2000/01/rdf-schema#comment | "Mu-conotoxins are small peptide inhibitors of muscle and neuronal tetrodotoxin (TTX)-sensitive voltage-gated sodium channels (VGSCs). Here we report the isolation of mu-conotoxins SIIIA and SIIIB by (125)I-TIIIA-guided fractionation of milked Conus striatus venom. SIIIA and SIIIB potently displaced (125)I-TIIIA from native rat brain Na(v)1.2 (IC(50) values 10 and 5 nm, respectively) and muscle Na(v)1.4 (IC(50) values 60 and 3 nm, respectively) VGSCs, and both inhibited current through Xenopus oocyte-expressed Na(v)1.2 and Na(v)1.4. An alanine scan of SIIIA-(2-20), a pyroglutamate-truncated analogue with enhanced neuronal activity, revealed residues important for affinity and selectivity. Alanine replacement of the solvent-exposed Trp-12, Arg-14, His-16, Arg-18 resulted in large reductions in SIIIA-(2-20) affinity, with His-16 replacement affecting structure. In contrast, [D15A]SIIIA-(2-20) had significantly enhanced neuronal affinity (IC(50) 0.65 nm), while the double mutant [D15A/H16R]SIIIA-(2-20) showed greatest Na(v)1.2 versus 1.4 selectivity (136-fold). (1)H NMR studies revealed that SIIIA adopted a single conformation in solution comprising a series of turns and an alpha-helical motif across residues 11-16 that is not found in larger mu-conotoxins. The structure of SIIIA provides a new structural template for the development of neuronally selective inhibitors of TTX-sensitive VGSCs based on the smaller mu-conotoxin pharmacophore."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m802852200"xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m802852200"xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Adams D.J."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Adams D.J."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Alewood P.F."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Alewood P.F."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Lewis R.J."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Lewis R.J."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Schroeder C.I."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Schroeder C.I."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Thomas L."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Thomas L."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Nielsen K.J."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Nielsen K.J."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Adams D."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Adams D."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Loughnan M.L."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Loughnan M.L."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Ekberg J."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/author | "Ekberg J."xsd:string |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18522941 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |