6x8r | pdb_00006x8r

Pharmacological characterisation and NMR structure of the novel mu-conotoxin SxIIIC, a potent irreversible NaV channel inhibitor

spinqualitylabelsall models 6x8r Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Ligands: NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Voltage-gated sodium (NaV) channel subtypes, including NaV1.7, are promising targets for the treatment of neurological diseases, such as chronic pain. Cone snail-derived micro-conotoxins are small, potent NaV channel inhibitors which represent potential drug leads. Of the 22 micro-conotoxins characterised so far, only a small number, including KIIIA and CnIIIC, have shown inhibition against human NaV1.7. We have recently identified a novel micro-conotoxin, SxIIIC, from Conus striolatus. Here we present the isolation of native peptide, chemical synthesis, characterisation of human NaV channel activity by whole-cell patch-clamp electrophysiology and analysis of the NMR solution structure. SxIIIC displays a unique NaV channel selectivity profile (1.4 > 1.3 > 1.1 approximately 1.6 approximately 1.7 > 1.2 >> 1.5 approximately 1.8) when compared to other micro-conotoxins and represents one of the most potent human NaV1.7 putative pore blockers (IC50 152.2 +/- 21.8 nM) to date. NMR analysis reveals the structure of SxIIIC includes the characteristic alpha-helix seen in other micro-conotoxins. Future investigations into structure-activity relationships of SxIIIC are expected to provide insights into residues important for NaV channel pore blocker selectivity and subsequently important for chronic pain drug development. Discovery, Pharmacological Characterisation and NMR Structure of the Novel micro-Conotoxin SxIIIC, a Potent and Irreversible NaV Channel Inhibitor.,McMahon KL, Tran HNT, Deuis JR, Lewis RJ, Vetter I, Schroeder CI Biomedicines. 2020 Oct 2;8(10). pii: biomedicines8100391. doi:, 10.3390/biomedicines8100391. PMID:33023152 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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