Suppr超能文献

PhTX-II,一种来自猪鼻蝰蛇毒液的具有肌肉毒性的碱性磷脂酶A₂,通过质谱法进行药理学特性鉴定和氨基酸序列分析。

PhTX-II a basic myotoxic phospholipase A₂ from Porthidium hyoprora snake venom, pharmacological characterization and amino acid sequence by mass spectrometry.

作者信息

Huancahuire-Vega Salomón, Ponce-Soto Luis Alberto, Marangoni Sergio

机构信息

Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, 13083-970 Campinas, SP, Brazil.

出版信息

Toxins (Basel). 2014 Oct 31;6(11):3077-97. doi: 10.3390/toxins6113077.

Abstract

A monomeric basic PLA₂ (PhTX-II) of 14149.08 Da molecular weight was purified to homogeneity from Porthidium hyoprora venom. Amino acid sequence by in tandem mass spectrometry revealed that PhTX-II belongs to Asp49 PLA₂ enzyme class and displays conserved domains as the catalytic network, Ca²⁺-binding loop and the hydrophobic channel of access to the catalytic site, reflected in the high catalytic activity displayed by the enzyme. Moreover, PhTX-II PLA₂ showed an allosteric behavior and its enzymatic activity was dependent on Ca²⁺. Examination of PhTX-II PLA₂ by CD spectroscopy indicated a high content of alpha-helical structures, similar to the known structure of secreted phospholipase IIA group suggesting a similar folding. PhTX-II PLA₂ causes neuromuscular blockade in avian neuromuscular preparations with a significant direct action on skeletal muscle function, as well as, induced local edema and myotoxicity, in mice. The treatment of PhTX-II by BPB resulted in complete loss of their catalytic activity that was accompanied by loss of their edematogenic effect. On the other hand, enzymatic activity of PhTX-II contributes to this neuromuscular blockade and local myotoxicity is dependent not only on enzymatic activity. These results show that PhTX-II is a myotoxic Asp49 PLA₂ that contributes with toxic actions caused by P. hyoprora venom.

摘要

从猪鼻蝰蛇毒液中纯化出一种分子量为14149.08 Da的单体碱性磷脂酶A₂(PhTX-II),纯度达到均一。串联质谱分析得到的氨基酸序列显示,PhTX-II属于Asp49磷脂酶A₂酶类,具有保守结构域,如催化网络、钙离子结合环以及通向催化位点的疏水通道,这体现在该酶所表现出的高催化活性上。此外,PhTX-II磷脂酶A₂表现出变构行为,其酶活性依赖于钙离子。通过圆二色光谱对PhTX-II磷脂酶A₂进行检测,结果表明其α-螺旋结构含量很高,这与分泌型磷脂酶IIA组的已知结构相似,提示其折叠方式类似。PhTX-II磷脂酶A₂可导致禽类神经肌肉制剂出现神经肌肉阻滞,对骨骼肌功能有显著直接作用,同时在小鼠中可诱发局部水肿和肌毒性。用溴酚蓝(BPB)处理PhTX-II会导致其催化活性完全丧失,同时水肿形成效应也消失。另一方面,PhTX-II的酶活性促成了这种神经肌肉阻滞,局部肌毒性不仅取决于酶活性。这些结果表明,PhTX-II是一种具有肌毒性的Asp49磷脂酶A₂,它对猪鼻蝰蛇毒液所引起的毒性作用有一定贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b6f/4247251/72679e015fb1/toxins-06-03077-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验