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SOLUTION STRUCTURE OF OMEGA-GRAMMOTOXIN SIA
Structural highlights
FunctionWGRTX_GRARO Inhibits P/Q- (Cav2.1/CACNA1A) and N-type (Cav2.2/CACNA1B) voltage-gated calcium channel by modifying voltage-dependent gating. It selectively and reversibly blocks the calcium channels coupled to glutamate release. Also inhibits potassium channels (Kv2.1/KCNB1) with lower affinity.[1] [2] [3] [4] [5] Publication Abstract from PubMedomega-Grammotoxin SIA (GrTx) is a 36 amino acid residue protein toxin from spider venom that inhibits P/Q and N-type voltage-gated Ca(2+) channels by modifying voltage-dependent gating. We determined the three-dimensional structure of GrTx using NMR spectroscopy. The toxin adopts an "inhibitor cystine knot" motif composed of two beta-strands (Leu19-Cys21 and Cys30-Trp32) and a beta-bulge (Trp6, Gly7-Cys30) with a +2x, -1 topology, which are connected by four chain reversals. Although GrTx was originally identified as an inhibitor of voltage-gated Ca(2+) channel, it also binds to K(+) channels with lower affinity. A similar cross-reaction was observed for Hanatoxin1 (HaTx), which binds to the voltage-sensing domains of K(+) and Ca(2+) channels with different affinities. A detailed comparison of the GrTx and HaTx structures identifies a conserved face containing a large hydrophobic patch surrounded by positively charged residues. The slight differences in the surface shape, which result from the orientation of the surface aromatic residues and/or the distribution of the charged residues, may explain the differences in the binding affinity of these gating modifiers with different voltage-gated ion channels. Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and N-type Ca(2+) channel.,Takeuchi K, Park E, Lee C, Kim J, Takahashi H, Swartz K, Shimada I J Mol Biol. 2002 Aug 16;321(3):517-26. PMID:12162963[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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