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Correlation of Venom Toxinome Composition of Indian Red Scorpion (Mesobuthus tamulus) with Clinical Manifestations of Scorpion Stings: Failure of Commercial Antivenom to Immune-Recognize the Abundance of Low Molecular Mass Toxins of This Venom.
Journal of Proteome Research ( IF 4.4 ) Pub Date : 2020-03-03 , DOI: 10.1021/acs.jproteome.0c00120
Bhabana Das 1 , Aparup Patra 1 , Ashis Kumar Mukherjee 1
Affiliation  

The Indian red scorpion (Mesobuthus tamulus), with its life-threatening sting, is the world's most dangerous species of scorpion. The toxinome composition of M. tamulus venom was determined by tandem mass spectrometry (MS) analysis of venom protein bands separated by SDS-PAGE. A total of 110 venom toxins were identified from searching the MS data against Buthidae family (taxid: 6855) of toxin entries in non-redundant protein databases. The Na+ and K+ ion channel toxins taken together are the most abundant toxins (76.7%) giving rise to the neurotoxic nature of this venom. The other minor toxin classes in the M. tamulus venom proteome are serine protease-like protein (2.9%), serine protease inhibitor (2.2%), antimicrobial peptide (2.3%), hyaluronidase (2.2%), makatoxin (2.1%), lipolysis potentiating peptides (1.2%), neurotoxin affecting Cl- channel (1%), parabutoporin (0.6%), Ca2+ channel toxins (0.8%), bradykinin potentiating peptides (0.2%), HMG CoA reductase inhibitor (0.1%) and other toxins with unknown pharmacological activity (7.7%). Several of these toxins have been shown to be promising drug candidates. M. tamulus venom does not show enzymatic activity (phospholipase A2, L-amino acid oxidase, adenosine tri-, di- and mono-phosphatase, hyaluronidase, metalloproteinase, and fibrinogenolytic), in vitro haemolytic activity, interference with blood coagulation, or platelet modulation properties. The clinical manifestations post M. tamulus sting have been described in the literature and are well correlated with its venom proteome composition. An abundance of low molecular mass toxins (3-15 kDa) are responsible for exerting the major pharmacological effects of M. tamulus venom though they are poorly immune-recognized by commercial scorpion antivenom. This is a major concern for the development of effective antivenom therapy against scorpion sting.

中文翻译:

印度红蝎(Mesobuthus tamulus)毒液毒素组的组成与蝎St的临床表现的关联:商业性毒液无法免疫-认识到该毒液的低分子毒素含量丰富。

印度红蝎(Mesobuthus tamulus)具有致命的刺痛,是世界上最危险的蝎子。通过串联质谱(MS)分析通过SDS-PAGE分离的毒液蛋白条带,测定鼠牙粘膜蛇毒的毒素组组成。通过针对非冗余蛋白质数据库中毒素条目的Buthidae家族(taxid:6855)的MS数据进行搜索,共鉴定出110种毒毒素。Na +和K +离子通道毒素合在一起是最丰富的毒素(76.7%),引起该毒液的神经毒性。鼠尾草毒液蛋白质组中的其他次要毒素类别是丝氨酸蛋白酶样蛋白(2.9%),丝氨酸蛋白酶抑制剂(2.2%),抗菌肽(2.3%),透明质酸酶(2.2%),麦卡毒素(2.1%),脂解增强肽(1.2%),神经毒素影响Cl通道(1%),副蛋白(0.6%),Ca2 +通道毒素(0.8%),缓激肽增强肽(0.2%),HMG CoA还原酶抑制剂(0.1%)和其他药理活性未知的毒素(7.7%) )。这些毒素中的几种已被证明是有前途的候选药物。鼠牙粘膜芽孢杆菌毒液没有酶活性(磷脂酶A2,L-氨基酸氧化酶,腺苷三,二和单磷酸腺苷,透明质酸酶,金属蛋白酶和纤维蛋白原分解酶),体外溶血活性,对凝血或血小板的干扰调制特性。在文献中已经描述了鼠牙轮虫st伤后的临床表现,并与其毒液蛋白质组组成密切相关。大量的低分子量毒素(3-15 kDa)引起了鼠牙粘膜蛇毒的主要药理作用,尽管它们对商业蝎子抗蛇毒血清的免疫识别能力很差。这是开发有效的抗蝎毒抗蛇毒疗法的主要问题。
更新日期:2020-04-24
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