2MYH

Omega-Tbo-IT1: selective inhibitor of insect calcium channels isolated from Tibellus oblongus spider venom

Summary for 2MYH

• Entry DOI: 10.2210/pdb2myh/pdb
• NMR Information: BMRB: 25452
• Descriptor: Omega-Tbo-IT1 toxin (1 entity in total)
• Functional Keywords: cystine knot inhibitor, ick, toxin
• Biological source: Tibellus oblongus
• Total number of polymer chains: 1
• Total formula weight: 4348.18

Authors

Altukhov, D.,Bozin, T.,Bocharov, E.,Kozlov, S.,Mikov, A. (deposition date: 2015-01-23, release date: 2015-12-09)

Primary citation

Mikov, A.N.,Fedorova, I.M.,Potapieva, N.N.,Maleeva, E.E.,Andreev, Y.A.,Zaitsev, A.V.,Kim, K.K.,Bocharov, E.V.,Bozin, T.N.,Altukhov, D.A.,Lipkin, A.V.,Kozlov, S.A.,Tikhonov, D.B.,Grishin, E.V.
omega-Tbo-IT1-New Inhibitor of Insect Calcium Channels Isolated from Spider Venom.
Sci Rep, 5:17232-17232, 2015

PubMed Abstract: Novel disulfide-containing polypeptide toxin was discovered in the venom of the Tibellus oblongus spider. We report on isolation, spatial structure determination and electrophysiological characterization of this 41-residue toxin, called ω-Tbo-IT1. It has an insect-toxic effect with LD50 19 μg/g in experiments on house fly Musca domestica larvae and with LD50 20 μg/g on juvenile Gromphadorhina portentosa cockroaches. Electrophysiological experiments revealed a reversible inhibition of evoked excitatory postsynaptic currents in blow fly Calliphora vicina neuromuscular junctions, while parameters of spontaneous ones were not affected. The inhibition was concentration dependent, with IC50 value 40 ± 10 nM and Hill coefficient 3.4 ± 0.3. The toxin did not affect frog neuromuscular junctions or glutamatergic and GABAergic transmission in rat brains. Ca(2+) currents in Calliphora vicina muscle were not inhibited, whereas in Periplaneta americana cockroach neurons at least one type of voltage gated Ca(2+) current was inhibited by ω-Tbo-IT1. Thus, the toxin apparently acts as an inhibitor of presynaptic insect Ca(2+) channels. Spatial structure analysis of the recombinant ω-Tbo-IT1 by NMR spectroscopy in aqueous solution revealed that the toxin comprises the conventional ICK fold containing an extended β-hairpin loop and short β-hairpin loop which are capable of making "scissors-like mutual motions".

PubMed: 26611444
DOI: 10.1038/srep17232

Experimental method

SOLUTION NMR