Fatty acylated toxin structure

Molecular Pharmacology of Voltage-Dependent Calcium Channels

“…In the search for potent toxins that inhibit neuronal Ca 21 channels in Dorosophila with much less sensitivity to major toxins such as w-CgTx-GVIA than those of vertebrates (68), presynaptic inhibitory activity was purified from the venom of the hunting spider Hololena curta (68) and Plectreurys tristes (69,70), using Drosophila neuromuscular junction as an assay. Both Hololena toxin (HoTx) (-50 nM) and Plectreurys toxin (PLTX) (^-10 nM) rapidly blocked Ca 21 currents measured in cultured neurons from dissociated embryos, although the two toxins differed in the extent of the block, the former eliminating only the non-inactivating component of the Ca 21 current and the latter inhibiting both the inactivating and non-inactivating component of the current (69,71).…”

“…The purified HoTX is composed of two different subunits of Mr 7,000 and 8,000 (68). HPLC purification and structural determination of one member of the PLTX family, PLTX-II, has revealed that PLTX-II is a 44-amino acid peptide with an O-palmitoyl threonine amide residue at its carboxy terminus (70). It is suggested that fatty acylation is required for the biological activity of the toxins, including PLTX-II because cleavage of the O-palmitoyl ester from the native toxin by base treatment results in a loss of biological activity.…”

Discovery and Structure of a Potent and Highly Specific Blocker of Insect Calcium Channels

“…While further experiments will clearly be required to test this hypothesis, it is salient to note that the insect calcium channel blocker PLTX-II from the spider Plectreurys tristis contains a C-terminal palmitoyl group that is essential for biological activity (36), and therefore it may function similarly. Thus, it will be instructive in future experiments to examine whether the C-terminal tail of -ACTX-Hv2a can be replaced by nonspecific hydrophobic anchors such as a palmitoyl group.…”

Lipid Masking and Reactivation of Angiotensin Analogues

“…Protein palmitoylation is associated with regulatory processes such as lateral diffusion, signaling, and receptor endocytosis [7]. Besides the thioester linkage, 0 -ester linkage has also been demonstrated, e.g., in toxins isolated from spider venoms [8] [9]. Generally, however, it has been shown that protein lipidation induces membrane association.…”