Natural Inhibitors of Snake Venom Metalloendopeptidases: History and Current Challenges.
Natural Inhibitors of Snake Venom Metalloendopeptidases: History and Current Challenges.
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DOI：
10.3390/toxins8090250
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发表时间：
2016-08-26
期刊：
影响因子：
4.2
通讯作者：
Valente RH
中科院分区：
文献类型：
--
作者：
Bastos VA;Gomes-Neto F;Perales J;Neves-Ferreira AG;Valente RH
天然蛇毒金属内肽酶抑制剂（SVMPI）的研究始于18世纪世纪，当时丰塔纳（Fontana）在研究蝰蛇对自身毒液的抗性方面做了开创性的工作。在过去的40年中，SVMPIs主要从耐药动物血清中分离得到，并得到不同程度的鉴定。它们是酸性寡聚糖蛋白，在广泛的pH值和温度值范围内保持生物活性。基于一级结构测定，哺乳动物血浆SVMPI被分类为免疫球蛋白（IG）超基因蛋白家族的成员，而从肌肉中分离的SVMPI属于纤维胶凝蛋白/调理素P35家族。另一方面，来自蛇血浆的SVMPI已被置于半胱氨酸蛋白酶抑制剂超家族中。这些天然抗毒素构成了对抗蛇毒的第一道防线，通过建立高亲和力的非共价相互作用来抑制蛇毒金属内肽酶的催化活性。本文回顾了自然抗性领域的历史，总结了其主要发现和当前挑战，这些挑战主要与使用“金标准”方法无法确定这些抑制剂的三维结构的局限性有关;提出了如何规避这些限制的观点。这些SVMPI在医学上的潜在应用也被强调。
The research on natural snake venom metalloendopeptidase inhibitors (SVMPIs) began in the 18th century with the pioneering work of Fontana on the resistance that vipers exhibited to their own venom. During the past 40 years, SVMPIs have been isolated mainly from the sera of resistant animals, and characterized to different extents. They are acidic oligomeric glycoproteins that remain biologically active over a wide range of pH and temperature values. Based on primary structure determination, mammalian plasmatic SVMPIs are classified as members of the immunoglobulin (Ig) supergene protein family, while the one isolated from muscle belongs to the ficolin/opsonin P35 family. On the other hand, SVMPIs from snake plasma have been placed in the cystatin superfamily. These natural antitoxins constitute the first line of defense against snake venoms, inhibiting the catalytic activities of snake venom metalloendopeptidases through the establishment of high-affinity, non-covalent interactions. This review presents a historical account of the field of natural resistance, summarizing its main discoveries and current challenges, which are mostly related to the limitations that preclude three-dimensional structural determinations of these inhibitors using “gold-standard” methods; perspectives on how to circumvent such limitations are presented. Potential applications of these SVMPIs in medicine are also highlighted.
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DOI：
10.1038/nrd1227
发表时间：
2003-11
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Acharya KR;Sturrock ED;Riordan JF;Ehlers MR
通讯作者：
Ehlers MR
影响因子：
2.9
作者：
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DOI：
10.1016/0304-4165(94)90080-9
发表时间：
1994-12-15
影响因子：
3
作者：
BORKOW, G;GUTIERREZ, JM;OVADIA, M
通讯作者：
OVADIA, M
影响因子：
120.1
作者：
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影响因子：
2.8
作者：
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