Munawar Aisha, Trusch Maria, Georgieva Dessislava, Spencer Patrick, Frochaux Violette, Harder Sönke, Arni Raghuvir K, Duhalov Deyan, Genov Nicolay, Schlüter Hartmut, Betzel Christian
Laboratory of Structural Biology of Infection and Inflammation, Institute of Biochemistry and Molecular Biology, University of Hamburg, Notkestr 85, Build 22a, 22603 Hamburg, Germany.
Mol Biosyst. 2011 Dec;7(12):3298-307. doi: 10.1039/c1mb05309d. Epub 2011 Sep 29.
Snake venom peptidomes are valuable sources of pharmacologically active compounds. We analyzed the peptidic fractions (peptides with molecular masses < 10,000 Da) of venoms of Vipera ammodytes meridionalis (Viperinae), the most toxic snake in Europe, and Bothrops jararacussu (Crotalinae), an extremely poisonous snake of South America. Liquid chromatography/mass spectrometry (LC/MS), direct infusion electrospray mass spectrometry (ESI-MS) and matrix-assisted desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were applied to characterize the peptides of both snake venoms. 32 bradykinin-potentiating peptides (BPPs) were identified in the Crotalinae venom and their sequences determined. 3 metalloproteinase inhibitors, 10 BPPs and a Kunitz-type inhibitor were observed in the Viperinae venom peptidome. Variability in the C-terminus of homologous BPPs was observed, which can influence the pharmacological effects. The data obtained so far show a subfamily specificity of the venom peptidome in the Viperidae family: BPPs are the major peptide component of the Crotalinae venom peptidome lacking Kunitz-type inhibitors (with one exception) while the Viperinae venom, in addition to BPPs, can contain peptides of the bovine pancreatic trypsin inhibitor family. We found indications for a post-translational phosphorylation of serine residues in Bothrops jararacussu venom BPP (S[combining low line]QGLPPGPPIP), which could be a regulatory mechanism in their interactions with ACE, and might influence the hypotensive effect. Homology between venom BPPs from Viperidae snakes and venom natriuretic peptide precursors from Elapidae snakes suggests a structural similarity between the respective peptides from the peptidomes of both snake families. The results demonstrate that the venoms of both snakes are rich sources of peptides influencing important physiological systems such as blood pressure regulation and hemostasis. The data can be used for pharmacological and medical applications.
蛇毒肽组是具有药理活性化合物的宝贵来源。我们分析了欧洲毒性最强的蛇——南欧蝰蛇（蝰亚科）和南美洲剧毒蛇——巴西矛头蝮（蝰蛇科）毒液的肽段部分（分子量<10,000 Da的肽）。采用液相色谱/质谱（LC/MS）、直接进样电喷雾质谱（ESI-MS）和基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF-MS）对两种蛇毒的肽进行表征。在蝰蛇科毒液中鉴定出32种缓激肽增强肽（BPPs）并确定了其序列。在蝰亚科蛇毒肽组中观察到3种金属蛋白酶抑制剂、10种BPPs和1种库尼茨型抑制剂。观察到同源BPPs C末端的变异性，这可能会影响药理作用。目前获得的数据显示蝰蛇科毒液肽组具有亚科特异性：BPPs是蝰蛇科毒液肽组的主要肽成分，缺乏库尼茨型抑制剂（有一个例外），而蝰亚科毒液除BPPs外，还可含有牛胰蛋白酶抑制剂家族的肽。我们发现巴西矛头蝮毒液BPP（S[带下划线]QGLPPGPPIP）中丝氨酸残基存在翻译后磷酸化的迹象，这可能是其与ACE相互作用的一种调节机制，可能会影响降压效果。蝰蛇科蛇毒BPPs与眼镜蛇科蛇毒利钠肽前体之间的同源性表明，这两个蛇科肽组中的相应肽在结构上具有相似性。结果表明，两种蛇的毒液都是影响血压调节和止血等重要生理系统的肽的丰富来源。这些数据可用于药理和医学应用。
