Non-disulfide-bridged peptide 43

BmK AS is a beta long-chain scorpion peptide from the venom of Buthus martensii Karsch (BmK). It was efficiently expressed as a soluble and functional peptide in Escherichia coli, and purified by metal chelating chromatography. About 4.2 mg/l purified recombinant BmK AS could be obtained. The recombinant BmK AS maintained a similar analgesic activity to the natural one in both the mouse-twisting test and hot-plate procedure. It also exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria. BmK AS is the first long-chain scorpion peptide reported to have antimicrobial activity, and is a valuable molecular scaffold for pharmacological research.

Among the different scorpion species, Buthus martensi Karsch (BmK), a widely distributed scorpion species in Asia, has received a lot of attention. Indeed, over the past decade, more than 70 different peptides, toxins or homologues have been isolated and more peptides are probably still to be revealed. This review is focusing on the many peptides isolated from the venom of this scorpion, their targets, their genes and their structures. The aim is to give both a 'state of the art' view of the research on BmK venom and an illustration of the complexity of this scorpion venom. In the present manuscript, we have listed the different ion channel toxins and homologues isolated from the venom of BmK, either from the literature or from databases. We have described here 51 long-chain peptides related to the Na(+) channel toxins family: 34 related to the alpha-toxin family, four related to the excitatory insect toxin family, 10 related to the depressant insect toxin, one beta-like toxin plus two peptides, BmK AS and AS1, that act on ryanodine receptors. We also listed 18 peptides related to the K(+) channel toxin family: 14 short chain toxins or homologues, two long chain K(+) toxin homologues and two putative K(+) toxin precursors. Additionally, two chlorotoxin like peptides (Bm-12 and 12 b) have been isolated in the venom of BmK. Besides these ion channels toxins, two peptides without disulfide bridges (the bradykinin-potentiating peptide BmK bpp and BmK n1) and three peptides with no known functions have also been discovered in this venom. We have also taken the opportunity of this review to update the classification of scorpion K(+) toxins () which now presents 17 subfamilies instead of the 12 described earlier. The work on the venom of BmK led to the discovery of two new subfamilies, alpha-KT x 14 and alpha-KT x 17.

Three insect neurotoxins from the scorpion Buthus martensii Karsch, named BmK I1, BmK I4 and BmK I6, have been purified and crystallized. BmK I1 and BmK I4 show strong toxicity to insects, while BmK I6 is relatively weaker. They all exhibit an evident analgesic effect on mice; this is a novel biological function for scorpion insect toxins. Their crystals diffract to at least 3.5 (BmK I1), 2.8 (BmK I4), 2.8 (BmK I6 crystal form I) and 2.2 A (of BmK I6 crystal form II) resolution on an ordinary X-ray source. Crystals of BmK I1 belong to space group P6, with unit-cell parameters a = b = 66.2, c = 176.7 A. BmK I4 crystallized in the tetragonal space group I4, with unit-cell parameters a = b = 134.5, c = 60.6 A. BmK I6 has been crystallized in two forms: form I belongs to space group C2, with unit-cell parameters a = 46.5, b = 85.2, c = 32.6 A, beta = 110.5 degrees; form II belongs to space group R3, with the hexagonal unit-cell parameters a = b = 44.5, c = 164.7 A.