2mvt

Solution structure of scoloptoxin SSD609 from Scolopendra mutilans

spinqualitylabelsall models 2mvt Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mvt is a 1 chain structure with sequence from Scolopendra subspinipes. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TX31A_SCODE Toxin that acts on KCNE1 and to a lesser extent KCNE3, the auxiliary subunits of potassium channel Kv7.1/KNCQ1 (PubMed:26307551). The toxin reversibly inhibits the slow delayed rectifier potassium currents (IKs) exhibited by the complex KCNQ1-KCNE1 (IC(50)=652 nM) and by the complex KCNQ1-KCNE3 (30% inhibition at 1 uM) (PubMed:26307551). The positively charged part of toxin binds to the negatively charged residues of the N-terminal amphipathic helix from the KCNE1 extracellular region (PubMed:26307551). Publication Abstract from PubMed KCNE1 is a single-span transmembrane auxiliary protein that modulates the voltage-gated potassium channel KCNQ1. The KCNQ1/KCNE1 complex in cardiomyocytes exhibited slow activated potassium (I(ks)) currents. Recently, a novel 47-residue polypeptide toxin SSD609 was purified from Scolopendra subspinipes dehaani venom and showed I(ks) current inhibition. Here, chemically synthesized SSD609 was shown to exert I(ks) inhibition in extracted guinea pig cardiomyocytes and KCNQ1/KCNE1 current attenuation in CHO cells. The K(+) current attenuation of SSD609 showed decent selectivity among different auxiliary subunits. Solution nuclear magnetic resonance analysis of SSD609 revealed a distinctive three-helix conformation that was stabilized by a new disulfide bonding pattern as well as segregated surface charge distribution. Structure-activity studies demonstrated that negatively charged Glu19 in the amphipathic extracellular helix of KCNE1 was the key residue that interacted with SSD609. The distinctive three-helix centipede toxin SSD609 is known to be the first polypeptide toxin acting on channel auxiliary subunit KCNE1, which suggests a new type of pharmacological regulation for ion channels in cardiomyocytes. A distinct three-helix centipede toxin SSD609 inhibits I(ks) channels by interacting with the KCNE1 auxiliary subunit.,Sun P, Wu F, Wen M, Yang X, Wang C, Li Y, He S, Zhang L, Zhang Y, Tian C Sci Rep. 2015 Aug 26;5:13399. doi: 10.1038/srep13399. PMID:26307551 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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