Novel Catalytically-Inactive PII Metalloproteinases from a Viperid Snake Venom with Substitutions in the Canonical Zinc-Binding Motif.
Novel Catalytically-Inactive PII Metalloproteinases from a Viperid Snake Venom with Substitutions in the Canonical Zinc-Binding Motif.
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DOI：
10.3390/toxins8100292
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发表时间：
2016-10-12
期刊：
影响因子：
4.2
通讯作者：
Rucavado A
中科院分区：
文献类型：
--
作者：
Camacho E;Sanz L;Escalante T;Pérez A;Villalta F;Lomonte B;Neves-Ferreira AG;Feoli A;Calvete JJ;Gutiérrez JM;Rucavado A
蛇毒金属蛋白酶（SVMPs）在猎物固定和消化过程中起着重要的生物学作用。这些活性中的大多数依赖于组织中相关蛋白质底物的水解。据此，我们描述了几种亚型和cDNA克隆序列，对应于PII SVMP同源物从毒液的中美洲蝮蛇Bothriechis lateralis，其中有修改的锌结合基序HEXXXHXXGXXH的典型序列的残基。因此，在偶氮酪蛋白和明胶上测试时，分离的蛋白质的蛋白水解活性是检测不到的。这些PII同种型在成熟蛋白中包含金属蛋白酶和去整合素结构域，因此属于SVMP的PIIb亚类。PII SVMP同系物没有出血和体外凝血活性，这些作用归因于SVMP的酶活性，但诱导轻度水肿。其中一种亚型在去整合素结构域中呈现特征性RGD序列，并抑制ADP和胶原诱导的血小板聚集。迄今为止，在蛇毒的表征中可能遗漏了无催化活性的SVMP同系物。蛇毒中是否存在这种无酶活性的同系物及其可能的毒性和适应性作用值得进一步研究。
Snake venom metalloproteinases (SVMPs) play key biological roles in prey immobilization and digestion. The majority of these activities depend on the hydrolysis of relevant protein substrates in the tissues. Hereby, we describe several isoforms and a cDNA clone sequence, corresponding to PII SVMP homologues from the venom of the Central American pit viper Bothriechis lateralis, which have modifications in the residues of the canonical sequence of the zinc-binding motif HEXXHXXGXXH. As a consequence, the proteolytic activity of the isolated proteins was undetectable when tested on azocasein and gelatin. These PII isoforms comprise metalloproteinase and disintegrin domains in the mature protein, thus belonging to the subclass PIIb of SVMPs. PII SVMP homologues were devoid of hemorrhagic and in vitro coagulant activities, effects attributed to the enzymatic activity of SVMPs, but induced a mild edema. One of the isoforms presents the characteristic RGD sequence in the disintegrin domain and inhibits ADP- and collagen-induced platelet aggregation. Catalytically-inactive SVMP homologues may have been hitherto missed in the characterization of snake venoms. The presence of such enzymatically-inactive homologues in snake venoms and their possible toxic and adaptive roles deserve further investigation.
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影响因子：
3.8
作者：
Escalante, T;Núñez, J;Gutiérrez, JM
通讯作者：
Gutiérrez, JM
影响因子：
4.8
作者：
Cornwall, GA;Hsia, N
通讯作者：
Hsia, N
影响因子：
2.8
作者：
GUTIERREZ, JM;ROMERO, M;OVADIA, M
通讯作者：
OVADIA, M
影响因子：
2.8
作者：
Fox, JW;Serrano, SMT
通讯作者：
Serrano, SMT
影响因子：
2.8
作者：
Calvete, JJ;Marcinkiewicz, C;Sanz, L
通讯作者：
Sanz, L