| http://purl.uniprot.org/citations/26817840 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26817840 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26817840 | http://www.w3.org/2000/01/rdf-schema#comment | "Cone snail toxins are well known blockers of voltage-gated sodium channels, a property that is of broad interest in biology and therapeutically in treating neuropathic pain and neurological disorders. Although most conotoxin channel blockers function by direct binding to a channel and disrupting its normal ion movement, conotoxin μO§-GVIIJ channel blocking is unique, using both favorable binding interactions with the channel and a direct tether via an intermolecular disulfide bond. Disulfide exchange is possible because conotoxin μO§-GVIIJ contains anS-cysteinylated Cys-24 residue that is capable of exchanging with a free cysteine thiol on the channel surface. Here, we present the solution structure of an analog of μO§-GVIIJ (GVIIJ[C24S]) and the results of structure-activity studies with synthetic μO§-GVIIJ variants. GVIIJ[C24S] adopts an inhibitor cystine knot structure, with two antiparallel β-strands stabilized by three disulfide bridges. The loop region linking the β-strands (loop 4) presents residue 24 in a configuration where it could bind to the proposed free cysteine of the channel (Cys-910, rat NaV1.2 numbering; at site 8). The structure-activity study shows that three residues (Lys-12, Arg-14, and Tyr-16) located in loop 2 and spatially close to residue 24 were also important for functional activity. We propose that the interaction of μO§-GVIIJ with the channel depends on not only disulfide tethering via Cys-24 to a free cysteine at site 8 on the channel but also the participation of key residues of μO§-GVIIJ on a distinct surface of the peptide."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m115.697672"xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m115.697672"xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Green B.R."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Green B.R."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Zhang M."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Zhang M."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Norton R.S."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Norton R.S."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Olivera B.M."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Olivera B.M."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Rivier J.E."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Rivier J.E."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Bulaj G."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Bulaj G."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Yoshikami D."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Yoshikami D."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Chhabra S."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Chhabra S."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Gajewiak J."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Gajewiak J."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Skalicky J.J."xsd:string |
| http://purl.uniprot.org/citations/26817840 | http://purl.uniprot.org/core/author | "Skalicky J.J."xsd:string |