Heck S D, Siok C J, Krapcho K J, Kelbaugh P R, Thadeio P F, Welch M J, Williams R D, Ganong A H, Kelly M E, Lanzetti A J
NPS Pharmaceuticals Incorporated, Salt Lake City, Utah 84108.
Science. 1994 Nov 11;266(5187):1065-8. doi: 10.1126/science.7973665.
The venom of the funnel-web spider Agelenopsis aperta contains several peptides that paralyze prey by blocking voltage-sensitive calcium channels. Two peptides, omega-Aga-IVB (IVB) and omega-Aga-IVC (IVC), have identical amino acid sequences, yet have opposite absolute configurations at serine 46. These toxins had similar selectivities for blocking voltage-sensitive calcium channel subtypes but different potencies for blocking P-type voltage-sensitive calcium channels in rat cerebellar Purkinje cells as well as calcium-45 influx into rat brain synaptosomes. An enzyme purified from venom converts IVC to IVB by isomerizing serine 46, which is present in the carboxyl-terminal tail, from the L to the D configuration. Unlike the carboxyl terminus of IVC, that of IVB was resistant to the major venom protease. These results show enzymatic activities in A. aperta venom being used in an unprecedented strategy for coproduction of necessary neurotoxins that possess enhanced stability and potency.
漏斗网蜘蛛（Agelenopsis aperta）的毒液含有几种通过阻断电压敏感性钙通道使猎物麻痹的肽。两种肽，ω-Aga-IVB（IVB）和ω-Aga-IVC（IVC），具有相同的氨基酸序列，但在丝氨酸46处具有相反的绝对构型。这些毒素对阻断电压敏感性钙通道亚型具有相似的选择性，但在大鼠小脑浦肯野细胞中阻断P型电压敏感性钙通道以及阻止钙-45流入大鼠脑突触体方面具有不同的效力。从毒液中纯化的一种酶通过将存在于羧基末端尾巴中的丝氨酸46从L构型异构化为D构型，将IVC转化为IVB。与IVC的羧基末端不同，IVB的羧基末端对主要的毒液蛋白酶具有抗性。这些结果表明，A. aperta毒液中的酶活性被用于一种前所未有的策略，用于共同产生具有增强稳定性和效力的必需神经毒素。
