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来自银环蛇毒液的钾通道阻滞剂β-银环蛇毒素具有抗原生动物活性。

The Potassium Channel Blocker β-Bungarotoxin from the Krait Venom Manifests Antiprotozoal Activity.

作者信息

Osipov Alexey V, Cheremnykh Elena G, Ziganshin Rustam H, Starkov Vladislav G, Nguyen Trang Thuy Thi, Nguyen Khoa Cuu, Le Dung Tien, Hoang Anh Ngoc, Tsetlin Victor I, Utkin Yuri N

机构信息

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.

Mental Health Research Centre, Moscow 115522, Russia.

出版信息

Biomedicines. 2023 Apr 7;11(4):1115. doi: 10.3390/biomedicines11041115.

DOI:10.3390/biomedicines11041115
PMID:37189733
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10136136/
Abstract

Protozoal infections are a world-wide problem. The toxicity and somewhat low effectiveness of the existing drugs require the search for new ways of protozoa suppression. Snake venom contains structurally diverse components manifesting antiprotozoal activity; for example, those in cobra venom are cytotoxins. In this work, we aimed to characterize a novel antiprotozoal component(s) in the krait venom using the ciliate as a model organism. To determine the toxicity of the substances under study, surviving ciliates were registered automatically by an original BioLaT-3.2 instrument. The krait venom was separated by three-step liquid chromatography and the toxicity of the obtained fractions against was analyzed. As a result, 21 kDa protein toxic to was isolated and its amino acid sequence was determined by MALDI TOF MS and high-resolution mass spectrometry. It was found that antiprotozoal activity was manifested by β-bungarotoxin (β-Bgt) differing from the known toxins by two amino acid residues. Inactivation of β-Bgt phospholipolytic activity with -bromophenacyl bromide did not change its antiprotozoal activity. Thus, this is the first demonstration of the antiprotozoal activity of β-Bgt, which is shown to be independent of its phospholipolytic activity.

摘要

原生动物感染是一个全球性问题。现有药物的毒性和有效性相对较低，这就需要寻找抑制原生动物的新方法。蛇毒含有结构多样的具有抗原生动物活性的成分；例如，眼镜蛇毒中的成分是细胞毒素。在这项研究中，我们旨在以纤毛虫为模式生物，鉴定银环蛇毒中的一种新型抗原生动物成分。为了确定所研究物质的毒性，通过一台原始的BioLaT - 3.2仪器自动记录存活的纤毛虫数量。银环蛇毒通过三步液相色谱法进行分离，并分析所得馏分对[此处原文缺失具体对象]的毒性。结果，分离出了一种对[此处原文缺失具体对象]有毒的21 kDa蛋白质，并通过基质辅助激光解吸电离飞行时间质谱（MALDI TOF MS）和高分辨率质谱法确定了其氨基酸序列。发现抗原生动物活性由β - 银环蛇毒素（β - Bgt）表现出来，它与已知毒素在两个氨基酸残基上有所不同。用对溴苯甲酰溴使β - Bgt的磷脂酶活性失活，并没有改变其抗原生动物活性。因此，这是首次证明β - Bgt的抗原生动物活性，且该活性被证明与其磷脂酶活性无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/9a1b42a06aa4/biomedicines-11-01115-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/d640df399734/biomedicines-11-01115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/48c68201082a/biomedicines-11-01115-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/2cb0ec210cae/biomedicines-11-01115-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/befb72f56ac0/biomedicines-11-01115-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/a841edf32165/biomedicines-11-01115-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/63ce772903dc/biomedicines-11-01115-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/dd63eb193578/biomedicines-11-01115-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/19de58f7305d/biomedicines-11-01115-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/9a1b42a06aa4/biomedicines-11-01115-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/d640df399734/biomedicines-11-01115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/48c68201082a/biomedicines-11-01115-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/2cb0ec210cae/biomedicines-11-01115-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/befb72f56ac0/biomedicines-11-01115-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/a841edf32165/biomedicines-11-01115-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/63ce772903dc/biomedicines-11-01115-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/dd63eb193578/biomedicines-11-01115-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/19de58f7305d/biomedicines-11-01115-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ec1/10136136/9a1b42a06aa4/biomedicines-11-01115-g009.jpg

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