1emx

SOLUTION STRUCTURE OF HPTX2, A TOXIN FROM HETEROPODA VENATORIA SPIDER VENOM THAT BLOCKS KV4.2 POTASSIUM CHANNEL

spinqualitylabelsall models 1emx Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1emx is a 1 chain structure with sequence from Heteropoda venatoria. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 26 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TXHP2_HETVE Inhibitor of voltage-gated potassium channels of the Kv4/KCND family. Inhibition of Kv4.3/KCND3 and Kv4.2/KCND2 is strongly voltage-dependent, while inhibition of Kv4.1/KCND1 shows less voltage-dependence. Its binding site may be near the potassium channel voltage sensor. Also blocks calcium channels. [REFERENCE:2] Publication Abstract from PubMed HpTX2 is a toxin from the venom of Heteropoda venatoria spider that has been demonstrated to bind on Kv4.2 potassium channel. We have determined the solution structure of recombinant HpTX2 by use of conventional two-dimensional NMR techniques followed by distance-geometry and molecular dynamics. The calculated structure belongs to the Inhibitory Cystin Knot structural family that consists in a compact disulfide-bonded core, from which four loops emerge. A poorly defined two-stranded antiparallel beta-sheet (residues 20-23 and 25-28) is detected. Analysis of the electrostatic charge anisotropy allows us to propose a functional map of HpTX2 different from the one described for kappa-conotoxin PVIIA, but strongly related to the one of charybdotoxin. The orientation of the dipole moment of HpTX2 emerges through K27 which could therefore be the critical lysine residue. Close to this lysine are a second basic residue, R23, an aromatic cluster (F7, W25, W30) and an hydrophobic side chain (L24). The high density in aromatic side chains of the putative functional surface as well as the lack of an asparagine is proposed to be the structural basis of the specificity of HpTX2 toward Kv4.2 channel. Solution structure of hpTX2, a toxin from Heteropoda venatoria spider that blocks Kv4.2 potassium channel.,Bernard C, Legros C, Ferrat G, Bischoff U, Marquardt A, Pongs O, Darbon H Protein Sci. 2000 Nov;9(11):2059-67. PMID:11152117 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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