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从斑蝥(鞘翅目,芫菁科)中分离的 Kunitz 型蛋白酶抑制剂的分子特征。

Molecular Characterization of Kunitz-Type Protease Inhibitors from Blister Beetles (Coleoptera, Meloidae).

机构信息

Department of Sciences, University of Roma Tre, 00146 Rome, Italy.

Division of Health Protection Technologies, Italian National Agency for Energy New Technologies and Sustainable Economic Development (ENEA), 00123 Rome, Italy.

出版信息

Biomolecules. 2022 Jul 15;12(7):988. doi: 10.3390/biom12070988.

Abstract

Protease inhibitors are widely studied since the unrestricted activity of proteases can cause extensive organ lesions. In particular, elastase activity is involved in the pathophysiology of acute lung injury, for example during SARS-CoV-2 infection, while serine proteases and thrombin-like proteases are involved in the development and/or pathology of the nervous system. Natural protease inhibitors have the advantage to be reversible and with few side effects and thus are increasingly considered as new drugs. Kunitz-type protease inhibitors (KTPIs), reported in the venom of various organisms, such as wasps, spiders, scorpions, and snakes, have been studied for their potent anticoagulant activity and widespread protease inhibitor activity. Putative KTPI anticoagulants have been identified in transcriptomic resources obtained for two blister beetle species, and . The KTPIs of and were characterized by combined transcriptomic and bioinformatics methodologies. The full-length mRNA sequences were divided on the base of the sequence of the active sites of the putative proteins. In silico protein structure analyses of each group of translational products show the biochemical features of the active sites and the potential protease targets. Validation of these genes is the first step for considering these molecules as new drugs for use in medicine.

摘要

蛋白酶抑制剂的研究非常广泛,因为蛋白酶的无限制活性会导致广泛的器官损伤。特别是弹性蛋白酶的活性与急性肺损伤的病理生理学有关,例如在 SARS-CoV-2 感染期间,而丝氨酸蛋白酶和类凝血酶蛋白酶则与神经系统的发展和/或病理学有关。天然蛋白酶抑制剂具有可逆性和副作用少的优点,因此越来越被视为新药。Kunitz 型蛋白酶抑制剂(KTPIs)存在于各种生物体的毒液中,如黄蜂、蜘蛛、蝎子和蛇,因其强大的抗凝活性和广泛的蛋白酶抑制剂活性而受到研究。在两种斑蝥属物种[1]和[2]的转录组资源中已经鉴定出潜在的 KTPI 抗凝剂。[1]和[2]的 KTPIs 采用组合转录组学和生物信息学方法进行了表征。全长 mRNA 序列根据假定蛋白的活性位点序列进行划分。每个翻译产物组的计算机蛋白质结构分析显示了活性位点的生化特征和潜在的蛋白酶靶标。这些基因的验证是将这些分子作为新药用于医学的第一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aea/9312475/d1edd3b1fe19/biomolecules-12-00988-g001.jpg

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