2lix

Solution structure Analysis of the ImKTx104

spinqualitylabelsall models 2lix Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2lix is a 1 chain structure with sequence from Lychas mucronatus. 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 KA281_ISOMC Publication Abstract from PubMed BACKGROUND: Although the basic scorpion K(+) channel toxins (KTxs) are well-known pharmacological tools and potential drug candidates, characterization the acidic KTxs still has the great significance for their potential selectivity towards different K(+) channel subtypes. Unfortunately, research on the acidic KTxs has been ignored for several years and progressed slowly. PRINCIPAL FINDINGS: Here, we describe the identification of nine new acidic KTxs by cDNA cloning and bioinformatic analyses. Seven of these toxins belong to three new alpha-KTx subfamilies (alpha-KTx28, alpha-KTx29, and alpha-KTx30), and two are new members of the known kappa-KTx2 subfamily. ImKTx104 containing three disulfide bridges, the first member of the alpha-KTx28 subfamily, has a low sequence homology with other known KTxs, and its NMR structure suggests ImKTx104 adopts a modified cystine-stabilized alpha-helix-loop-beta-sheet (CS-alpha/beta) fold motif that has no apparent alpha-helixs and beta-sheets, but still stabilized by three disulfide bridges. These newly described acidic KTxs exhibit differential pharmacological effects on potassium channels. Acidic scorpion toxin ImKTx104 was the first peptide inhibitor found to affect KCNQ1 channel, which is insensitive to the basic KTxs and is strongly associated with human cardiac abnormalities. ImKTx104 selectively inhibited KCNQ1 channel with a K(d) of 11.69 microM, but was less effective against the basic KTxs-sensitive potassium channels. In addition to the ImKTx104 toxin, HeTx204 peptide, containing a cystine-stabilized alpha-helix-loop-helix (CS-alpha/alpha) fold scaffold motif, blocked both Kv1.3 and KCNQ1 channels. StKTx23 toxin, with a cystine-stabilized alpha-helix-loop-beta-sheet (CS-alpha/beta) fold motif, could inhibit Kv1.3 channel, but not the KCNQ1 channel. CONCLUSIONS/SIGNIFICANCE: These findings characterize the structural and functional diversity of acidic KTxs, and could accelerate the development and clinical use of acidic KTxs as pharmacological tools and potential drugs. Structural and functional diversity of acidic scorpion potassium channel toxins.,Chen ZY, Zeng DY, Hu YT, He YW, Pan N, Ding JP, Cao ZJ, Liu ML, Li WX, Yi H, Jiang L, Wu YL PLoS One. 2012;7(4):e35154. Epub 2012 Apr 12. PMID:22511981 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Potassium channel toxin 3D structures

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