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Protease Inhibitors from Marine Venomous Animals and Their Counterparts in Terrestrial Venomous Animals
Laboratory of Toxinology, Department of Physiological Sciences, University of Brasília, Brasília, DF, 70910-900, Brazil
* Author to whom correspondence should be addressed.
Received: 19 April 2013; in revised form: 28 May 2013 / Accepted: 30 May 2013 / Published: 14 June 2013
Abstract: The Kunitz-type protease inhibitors are the best-characterized family of serine protease inhibitors, probably due to their abundance in several organisms. These inhibitors consist of a chain of ~60 amino acid residues stabilized by three disulfide bridges, and was first observed in the bovine pancreatic trypsin inhibitor (BPTI)-like protease inhibitors, which strongly inhibit trypsin and chymotrypsin. In this review we present the protease inhibitors (PIs) described to date from marine venomous animals, such as from sea anemone extracts and Conus venom, as well as their counterparts in terrestrial venomous animals, such as snakes, scorpions, spiders, Anurans, and Hymenopterans. More emphasis was given to the Kunitz-type inhibitors, once they are found in all these organisms. Their biological sources, specificity against different proteases, and other molecular blanks (being also K+ channel blockers) are presented, followed by their molecular diversity. Whereas sea anemone, snakes and other venomous animals present mainly Kunitz-type inhibitors, PIs from Anurans present the major variety in structure length and number of Cys residues, with at least six distinguishable classes. A representative alignment of PIs from these venomous animals shows that, despite eventual differences in Cys assignment, the key-residues for the protease inhibitory activity in all of them occupy similar positions in primary sequence. The key-residues for the K+ channel blocking activity was also compared.
Keywords: protease inhibitor; Kunitz-type; serine protease; toxin; trypsin; chymotrypsin; venom
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MDPI and ACS Style
Mourão, C.B.F.; Schwartz, E.F. Protease Inhibitors from Marine Venomous Animals and Their Counterparts in Terrestrial Venomous Animals. Mar. Drugs 2013, 11, 2069-2112.
Mourão CBF, Schwartz EF. Protease Inhibitors from Marine Venomous Animals and Their Counterparts in Terrestrial Venomous Animals. Marine Drugs. 2013; 11(6):2069-2112.
Mourão, Caroline B.F.; Schwartz, Elisabeth F. 2013. "Protease Inhibitors from Marine Venomous Animals and Their Counterparts in Terrestrial Venomous Animals." Mar. Drugs 11, no. 6: 2069-2112.