1k64

NMR Structue of alpha-conotoxin EI

spinqualitylabelsall models 1k64 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1k64 is a 1 chain structure with sequence from Conus ermineus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: HYP, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CA1A_CONER Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. Probable competitive antagonist of fish muscle acetylcholine receptor (PubMed:32245200). Inhibits postsynaptic nicotinic acetylcholine receptors (nAChRs) from zebrafish (IC(50)=58-100 nM) (PubMed:32245200). Blocks mammalian nAChR composed of alpha-1/gamma and alpha-1/delta subunits. Blocks central nervous system nAChR composed of alpha-4-beta-2/CHRNA4-CHRNB2 subunits and peripheral nervous system nAChR composed of alpha-3-beta-4/CHRNA3-CHRNB4 subunits. Low toxin concentrations potentiate currents in muscle nAChR composed of alpha-1-beta-1-gamma-delta (CHRNA1-CHRNB1-CHRNG-CHRND) subunits and central nervous system nAChR composed of alpha-4-beta-2/CHRNA4-CHRNB2 subunits, but not peripheral nervous system nAChR composed of alpha-3-beta-4 subunits. Also exhibits inhibition of D.melanogaster alpha-7/CHRNA7 nAChRs (PubMed:25466886). Has possibly a distinct nAChR binding mode from other alpha-conotoxins, due to a different three residue motif (lacks the Ser-Xaa-Pro motif) (By similarity).[UniProtKB:Q2I2R8] Publication Abstract from PubMed A high resolution structure of alpha-conotoxin EI has been determined by (1)H NMR spectroscopy and molecular modeling. alpha-Conotoxin EI has the same disulfide framework as alpha 4/7 conotoxins targeting neuronal nicotinic acetylcholine receptors but antagonizes the neuromuscular receptor as do the alpha 3/5 and alpha A conotoxins. The unique binding preference of alpha-conotoxin EI to the alpha(1)/delta subunit interface of Torpedo neuromuscular receptor makes it a valuable structural template for superposition of various alpha-conotoxins possessing distinct receptor subtype specificities. Structural comparison of alpha-conotoxin EI with the gamma-subunit favoring alpha-conotoxin GI suggests that the Torpedo delta-subunit preference of the former originates from its second loop. Superposition of three-dimensional structures of seven alpha-conotoxins reveals that the estimated size of the toxin-binding pocket in nicotinic acetylcholine receptor is approximately 20 A (height) x 20 A (width) x 15 A (thickness). Solution conformation of alpha-conotoxin EI, a neuromuscular toxin specific for the alpha 1/delta subunit interface of torpedo nicotinic acetylcholine receptor.,Park KH, Suk JE, Jacobsen R, Gray WR, McIntosh JM, Han KH J Biol Chem. 2001 Dec 28;276(52):49028-33. Epub 2001 Oct 18. PMID:11641403 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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