A unique feature of the venom of Micrurus fulvius (Eastern coral snake) is its ability to induce severe intravascular hemolysis in particular species, such as dogs or mice. This effect was previously shown to be induced by distinct phospholipase A2 (PLA2) isoforms which cause direct hemolysis in vitro, an uncommon finding for such enzymes. The functional profiles of PLA2-17, a direct hemolytic enzyme, and PLA2-12, a co-existing venom isoform lacking such effect, were compared. The enzymes differed not only in their ability to cause intravascular hemolysis: PLA2-17 additionally displayed lethal, myotoxic, and anticoagulant actions, whereas PLA2-12 lacked these effects. PLA2-12 was much more active in hydrolyzing a monodisperse synthetic substrate than PLA2-17, but the catalytic activity of latter was notably higher on a micellar substrate, or towards pure phospholipid artificial monolayers under controlled lateral pressures. Interestingly, PLA2-17 could hydrolyze substrate at a pressure of 20 mN m-1, in contrast to PLA2-12 or the non-toxic pancreatic PLA2. This suggests important differences in the monolayer penetrating power, which could be related to differences in toxicity. Comparative examination of primary structures and predicted three-dimensional folding of PLA2-12 and PLA2-17, revealed that differences concentrate in their N-terminal and central regions, leading to variations of the surface properties at the membrane interacting interface. PLA2-17 presents a less basic interfacial surface than PLA2-12, but more bulky aromatic residues, which could be associated to its higher membrane-penetrating strength. Altogether, these structural and functional comparative observations suggest that the ability of PLA2s to penetrate substrate interfaces could be a major determinant of toxicity, perhaps more important than protein surface charge.

中文翻译：

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来自东方珊瑚蛇毒液的磷脂酶 A 2 诱导的血管内溶血，Micrurus fulvius：溶血和非溶血同种型的功能特征

Micrurus fulvius（东方珊瑚蛇）毒液的一个独特特征是它能够在特定物种（例如狗或老鼠）中引起严重的血管内溶血。先前已证明这种效应是由不同的磷脂酶 A2 (PLA2) 同工型诱导的，这些同工型在体外引起直接溶血，这种酶的发现并不常见。比较了直接溶血酶 PLA2-17 和缺乏这种作用的共存毒液同种型 PLA2-12 的功能特征。这些酶不仅在引起血管内溶血的能力上有所不同：PLA2-17 还显示出致死、肌毒性和抗凝作用，而 PLA2-12 则没有这些作用。PLA2-12 在水解单分散合成底物方面比 PLA2-17 更活跃，但后者在胶束底物上的催化活性明显更高，或在受控侧向压力下形成纯磷脂人工单层。有趣的是，与 PLA2-12 或无毒胰腺 PLA2 相比，PLA2-17 可以在 20 mN m-1 的压力下水解底物。这表明单层穿透能力的重要差异，这可能与毒性差异有关。PLA2-12 和 PLA2-17 的初级结构和预测的三维折叠的比较检查表明，差异集中在它们的 N 端和中心区域，导致膜相互作用界面的表面特性发生变化。与 PLA2-12 相比，PLA2-17 的界面碱性较低，但具有更大的芳香族残基，这可能与其更高的膜穿透强度有关。共，