1scy

From Proteopedia

DETERMINATION OF THE THREE-DIMENSIONAL STRUCTURE OF SCYLLATOXIN BY 1H NUCLEAR MAGNETIC RESONANCE

PDB ID 1scy

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Structural highlights

1scy is a 1 chain structure with sequence from Leiurus quinquestriatus hebraeus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KAX51_LEIHE Blocker for the small conductance calcium-activated potassium channels (PubMed:2839478, PubMed:2307683, PubMed:11527975). Shows the best affinity for KCa2.2/KCNN2 (Kd=0.2 nM), followed by KCa2.3/KCNN3 (Kd=1.1 nM) and KCa2.1/KCNN1 (Kd=325 nM) (PubMed:11527975).^[1] ^[2] ^[3]

Publication Abstract from PubMed

The three-dimensional solution structure of Scyllatoxin (leiurotoxin I) a venom peptide from the scorpion Leiurus quinquestriatus hebraeus was determined at 1 A resolution by homonuclear proton n.m.r. methods at 500 MHz. Data analysis and structure calculation followed conventional protocols inherent to DIANA and related programs with two exceptions. First, distance constraints were obtained from two-dimensional nuclear Overhauser spectra by a previously described partial relaxation matrix approach. Second, since the pairing pattern of the six cysteine residues was not established a priori, the unequivocal assignment of the disulfide bridges was achieved exclusively from the n.m.r. data by a statistical analysis of preliminary DIANA structures. In the final calculation we used 227 upper distance constraints, 67 torsional constraints from vicinal coupling constants and ten stereospecific assignments of beta-methylene protons. Scyllatoxin folds into a compact ellipsoidal shape. An alpha-helix (defined with 0.24 A resolution) spanning 2.5 turns from Leu5 till Ser14 is stabilized by Cys8-Cys26 and Cys12-Cys28 disulfide bridges to the carboxy-terminal strand of an anti-parallel beta-sheet. The antiparallel beta-sheet (defined at 0.66 A resolution) extends from Leu18 to Val29 with a tight turn at Gly23-Asp24 and displays a right-handed twist. Scyllatoxin competes with the toxins apamin from Apis mellifera mellifera and P05 from Androctonus mauretanicus mauretanicus for the same or similar high conductance calcium-activated potassium channels. Consideration of presently known biological activities and three-dimensional structures of these toxins suggest a different toxin-receptor interaction of scyllatoxin as compared to apamin and P05.

Determination of the three-dimensional solution structure of scyllatoxin by 1H nuclear magnetic resonance.,Martins JC, Van de Ven FJ, Borremans FA J Mol Biol. 1995 Nov 3;253(4):590-603. PMID:7473736^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shakkottai VG, Regaya I, Wulff H, Fajloun Z, Tomita H, Fathallah M, Cahalan MD, Gargus JJ, Sabatier JM, Chandy KG. Design and characterization of a highly selective peptide inhibitor of the small conductance calcium-activated K+ channel, SkCa2. J Biol Chem. 2001 Nov 16;276(46):43145-51. PMID:11527975 doi:10.1074/jbc.M106981200
↑ Auguste P, Hugues M, Gravé B, Gesquière JC, Maes P, Tartar A, Romey G, Schweitz H, Lazdunski M. Leiurotoxin I (scyllatoxin), a peptide ligand for Ca2(+)-activated K+ channels. Chemical synthesis, radiolabeling, and receptor characterization. J Biol Chem. 1990 Mar 15;265(8):4753-9 PMID:2307683
↑ Chicchi GG, Gimenez-Gallego G, Ber E, Garcia ML, Winquist R, Cascieri MA. Purification and characterization of a unique, potent inhibitor of apamin binding from Leiurus quinquestriatus hebraeus venom. J Biol Chem. 1988 Jul 25;263(21):10192-7 PMID:2839478
↑ Martins JC, Van de Ven FJ, Borremans FA. Determination of the three-dimensional solution structure of scyllatoxin by 1H nuclear magnetic resonance. J Mol Biol. 1995 Nov 3;253(4):590-603. PMID:7473736 doi:http://dx.doi.org/S0022-2836(85)70575-X