期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 72, 期 -, 页码 158-162出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2014.08.010
关键词
cDNA libraries; Molecular diversity; Ascaris-type toxin
资金
- National Natural Sciences Foundation of China [31200557]
- National High Technology Research and Development Program of China [2012AA020304]
- Scientific Research Foundation for Doctors, Hubei University of Medicine [2013QDJZR02]
- New Century Excellent Talents in Wuhan University by the Ministry of Education of China [NCET-10-0651]
- Wuhan City Science and Technology Foundation of China [2013070204020046]
Serine protease inhibitors have been widely discovered from different animal venoms, but most of them belong to Kunitz-type toxin subfamily. Here, by screening scorpion venom gland cDNA libraries, we identified four new non-Kunitz serine protease inhibitors with a conserved Ascaris-type structural fold: Ascaris-type toxins Lychas mucronatus Ascaris-type protease inhibitor (LmAPI), Pandinus cavimanus Ascaris-type protease inhibitor (PcAPI), Pandinus cavimanus Ascaris-type protease inhibitor 2 (PcAPI-2), and Hottentotta judaicus Ascaris-type protease inhibitor (HjAPI). The detailed characterization of one Ascaris-type toxin LmAPI was further carried out, which contains 60 residues and possesses a classical Ascaris-type cysteine framework reticulated by five disulfide bridges. Enzyme and inhibitor reaction kinetics experiments showed that recombinant LmAPI inhibits the activity of chymotrypsin potently with a Ki value of 15.5 nM, but has little effect on trypsin and elastase. Bioinformatics analyses suggested that LmAPI contains unique functional residues TQD and might be a useful template to produce specific protease inhibitors. Our results indicated that animal venoms are a natural source of new type of protease inhibitors, which will accelerate the development of diagnostic and therapeutic agents for human diseases that target diverse proteases. (C) 2014 Elsevier B.V. All rights reserved.
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