Solution Structure of Two New Toxins from the Venom of the Chinese Scorpion Buthus martensi Karsch Blockers of Potassium Channels^,

Abstract

The solution structure of BmTX2 purified from the venom of the Chinese Buthid Buthus martensi has been determined by 2D NMR spectroscopy techniques which led to the description of its 3D conformation. The structure consists of a triple-stranded beta-sheet connected to a helical structure. This helix encompasses 10 residues, from 11 to 20, begins with a turn of 310 helix, and ends with an alpha helix. The three strands of beta sheet comprise residues 2-6, with a bulge covering residues 4 and 5, 26-29, and 32-35, with a type I' beta turn centered on residues 30-31. We also characterized the solution structure of BmTX1. The two toxins which are potent blockers of both large-conductance calcium-activated potassium channels (BKCa channels) and voltage-gated potassium channels (Kv1. 3) are highly superimposable and possess the same structural characteristics. Analysis of these structures allows us to hypothesize that, besides the main surface of interaction described by the functional map of charybdotoxin, one can expect that the binding of scorpion toxins on BKCa channels may involve residues on the edge of this surface.

Hydramacin-1, Structure and Antibacterial Activity of a Protein from the Basal Metazoan Hydra

“…Conserved residues within the macin-protein family are marked in gray. HM-1, hydramacin-1; TM, theromacin (7); NM, neuromacin (8); I, Mediterranean mussel defensin (MGD-1) (32); II, N. alata plant defensin 1 (NaD1) (27); PhD1, P. hybrida defensin 1 (26); III, Buthus marten's toxin 1 (BmTX1) (33); IV, heliomicin (34); V, Centruroides sculpturatus Ewing variant 2 toxin (CsE-v2) (35).…”

Solid‐Phase Synthesis and Biological Activity of a Thioether Analogue of Conotoxin G1

“…By introducing multiple disulfide bridges into short peptide sequences, nature has devised a unique class of biologically active molecules that are able to adopt well‐defined three‐dimensional structures because of the conformational stability conferred by these disulfide bridges. These highly potent and specific toxins, found in the venom of cone snails,4 spiders,5 scorpions,6 snakes,7 and lizards,8 target the ion channels9 and cell‐surface receptors in the neurological system, which results in reduced or blocked neurotransmission and causes paralysis and sometimes death. These neurotoxins have become interesting as biological probes and drug discovery leads10–15 because ion channels in particular are crucial to many biological processes, such as nerve transmission, hormone secretion, and the generation of cellular energy 16.…”

Macin Family of Antimicrobial Proteins Combines Antimicrobial and Nerve Repair Activities

“…Again, this may be further corroborated by a rational chimeric protein design as performed with the human ␤-defensins 2 and 3 (3). (33), Nicotiana alata plant defensin 1 (NaD1) (34), Buthus martensi toxin 1 (BmTX1) (35), heliomicin (Helio.) (36), and Centruroides sculpturatus Ewing variant 2 toxin (CsE-v2) (37).…”

“…3, B and C). In the case of hydramacin-1/neuromacin, most of the conserved residues (Glu 33 , Leu 34 , Gly 35 , and Tyr 60 ) are allocated to the highly defined region of the molecule (Fig. 3B).…”