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Functional characterization of a new non-Kunitz serine protease inhibitor from the scorpion Lychas mucronatus
Functional characterization of a new non-Kunitz serine protease inhibitor from the scorpion Lychas mucronatus
- Source :
- International Journal of Biological Macromolecules. 72:158-162
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- 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.
- Subjects :
- Protein Folding
Proteases
Serine Proteinase Inhibitors
Protein Conformation
medicine.medical_treatment
Scorpion Venoms
Biology
Biochemistry
Scorpions
Structural Biology
medicine
Animals
Humans
Amino Acid Sequence
Molecular Biology
Gene Library
chemistry.chemical_classification
Serine protease
Protease
Chymotrypsin
Kunitz STI protease inhibitor
General Medicine
Trypsin
Molecular biology
Enzyme
chemistry
biology.protein
Sequence Alignment
MASP1
medicine.drug
Subjects
Details
- ISSN :
- 01418130
- Volume :
- 72
- Database :
- OpenAIRE
- Journal :
- International Journal of Biological Macromolecules
- Accession number :
- edsair.doi.dedup.....e40221377e0482bc31b20043e56787a4
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2014.08.010