A Review of the Most Important Classes of Serine Protease Inhibitors in Insects and Leeches

Abstract

The constant increase of life expectancy is associated with major aging of developed populations. This indicates that the new century will have one of most epidemic progressions of cardiovascular, cancer and inflammatory diseases. The high challenge for medical research is to compress such morbidity. Invertebrates have demonstrated to be truly useful models in drug discovery for such aging diseases. The last decade, drug discovery in leeches has opened the gate for new molecules to treat emphysema, coagulation, inflammation, dermatitis and cancer. Also other invertebrates, such as insects, harvest potential interesting molecules, such as serine protease inhibitors that can be exploited by the medical industry. In this review we discuss the most important classes of serine protease inhibitors in insects and leeches.

Disk abalone (Haliotis discus discus) expresses a novel antistasin-like serine protease inhibitor: Molecular cloning and immune response against bacterial infection

“…In the P1 site of the antistasin domains, methionine occupied sites in the 3rd, 8th, and 9th domains, lysine in the 5th and 7th domains, arginine in the 2nd domain, and threonine in the 4th domain. It has been reported that bulky and aromatic residues such as phenylalanine, tyrosine, methionine or leucine residues are required for chymotrypsin inhibitor activity, whereas basic residues such as lysine and arginine are required for trypsin inhibitors [46]. Interestingly, in contrast to previously reported antistasin-type proteins, Ab-Antistasin is the first antistasin-type inhibitor, containing a phenylalanine residue at its predicted P1-residue; however, no significant chymotrypsin inhibitory activity was observed in this study.…”

“…Interestingly, the common feature of most of the PIs, the hydrophobic N-terminal domain which represents signal peptide, was not observed in Ab-Antistasin. Similarly, SPI serpin-2 of Manduca sexta [48], two serpin sequences of Anopheles gambiae (AJ271353 and AJ271352) and Drosophila serpin-4 [49] do not contain signal peptides, and were not present in the plasma [46]. Moreover, the N-glycosylation site at 349 NDSN 352 was observed in the sequence.…”

Production of an alkaline protease using Bacillus pumilus D3 without inactivation by SDS, its characterization and purification

“…All living organisms require proteases which play a significant role in various vital physiological processes such as food digestion, blood clotting, transcription control, growth factor secretion, embryogenesis, wound healing, cell migration, cell signaling, regeneration, molting, metamorphosis, defense mechanisms and immune responses 3 . Proteases are one of the most important enzymes for industries such as detergent, textile, pharmaceuticals.…”

Rock bream (Oplegnathus fasciatus) serpin, protease nexin-1: Transcriptional analysis and characterization of its antiprotease and anticoagulant activities

“…The endogenous Serine protease inhibitors (SERPINs) found universally in all domains of life including viruses (Clynen et al, 2005;Irving et al, 2000;Kang et al, 2006;Rawlings et al, 2004;Roberts and Hejgaard, 2008) that form the largest superfamily of serine protease inhibitors (Irving et al, 2000), control both intracellular and extracellular proteolytic pathways, which are very critical for hemeostasis, coagulation, complement activation, fibrinolysis and immune defense (Mangan et al, 2008;Rau et al, 2007). Our understanding of SERPIN biology from the reviews (16 clades, A-P) (Irving et al, 2000;Law et al, 2006;Silverman et al, 2001) continues to expand as new family members are added to the MEROPS database (http://merops.sanger.ac.uk/) (I4 family) (Rawlings et al, 2004).…”