1KOZ

SOLUTION STRUCTURE OF OMEGA-GRAMMOTOXIN SIA

Summary for 1KOZ

• Entry DOI: 10.2210/pdb1koz/pdb
• Descriptor: Voltage-dependent Channel Inhibitor (1 entity in total)
• Functional Keywords: toxin, cystine knot
• Cellular location: Secreted: P60590
• Total number of polymer chains: 1
• Total formula weight: 4122.78

Authors

Takeuchi, K.,Park, E.J.,Lee, C.W.,Kim, J.I.,Takahashi, H.,Swartz, K.J.,Shimada, I. (deposition date: 2001-12-25, release date: 2002-08-28, Last modification date: 2024-10-16)

Primary citation

Takeuchi, K.,Park, E.,Lee, C.,Kim, J.,Takahashi, H.,Swartz, K.,Shimada, I.
Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and N-type Ca(2+) channel.
J.Mol.Biol., 321:517-526, 2002

PubMed Abstract: omega-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.

PubMed: 12162963
DOI: 10.1016/S0022-2836(02)00595-8

Experimental method

SOLUTION NMR