The X-ray structure of a snake venom Gln48 phospholipase A₂ at 1.9Å resolution reveals anion-binding sites

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• 作者：Georgieva ; Dessislava Nikolova ; Perbandt ; Markus ; Rypniewski ; Wojciech ; Hristov ; Krassimir ; et. al.
• 关键词：X-ray structure ; Phospholipase A₂ ; Neurotoxin ; Snake venom
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：March 26, 2004
• 年：2004
• 卷：316
• 期：1
• 页码：33-38
• 全文大小：1008 K

文摘

Phospholipase A₂ is an “interfacial” enzyme and its binding to negatively charged surfaces is an important step during catalysis. The Gln48 phospholipase A₂ from the venom of Vipera ammodytes meridionalis plays the role of chaperone and directs a toxic His48 PLA₂ onto its acceptor. In the venom the two phospholipases A₂ exist as a postsynaptic neurotoxic complex, Vipoxin. The X-ray structure of Gln48 PLA₂, complexed to sulphate ions, which mimic the negatively charged groups of anionic membranes, has been determined by the molecular replacement method and refined to 1.9Å resolution. The protein forms a homodimer stabilized by ionic, hydrophobic, and hydrogen-bond interactions. The structure reveals two anion-binding sites per subunit. These sites are probably involved in interactions with the negatively charged membrane surface and, in this way, in the “targeting” of the toxic component to the receptors of the postsynaptic membranes. In the absence of the chaperone subunit the toxin changes the target of the physiological attack. A comparison of the homodimeric Gln48 PLA₂ structure with that of the heterodimeric Vipoxin reveals differences in regions involved in the pharmacological activity of the toxin. This fact, except the active site histidine substitution, can explain the absence of toxicity in the Gln48 protein in comparison to the His48 phospholipase A₂.