Boreskov

PP‐33BIOLOGICAL INPUT OF PROTEASE DIVERSITYNemova N.N. and Lysenko L.A.Institute of Biology, Karelian Research Centre of Russian Academy of Science,Petrozavodsk, RussiaProteases are enzymes that are essential for all live organisms. They cut up biologicalpolymers acting on peptide bonds (“biology’s version of Swiss army knives”, according toSeife, 1997). Proteases regulate the fate, localization, and activity of many proteins,modulate protein‐protein interactions, create new bioactive molecules, contribute to theprocessing of cellular information, thus generating, transducing, and amplifying molecularsignals. As a direct result of these multiple actions, different proteases are known to play keyroles in multiple biological processes, including cell cycle progression, differentiation andmigration, heat shock and unfolded protein responses, morphogenesis and tissueremodeling, neuronal outgrowth, angiogenesis, immunity, haemostasis, wound healing,ovulation, fertilization, autophagy, senescence, necrosis, and apoptosis (López‐Otín, Bond,2008). Proteases are also essential in viruses, bacteria and parasites promoting theirreplication and invasiveness, and on the other hand in hosts for the mediation andsustenance of diseases (Turk, 2006).The biological significance of proteolysis has driven the evolutionary invention ofmultiple, extremely diverse types and families of proteases. Through evolution, proteaseshave adapted to the wide range of conditions found in complex organisms (variable pH,reductive environment and so on) (Nemova, Bondareva, 2008). Despite proteases share acommon biochemical function, their catalytic domains exhibit sequence diversity. On thebasis of the mechanism of catalysis, depending on critical amino acid residues in active siteproteases are classified into seven distinct types: serine, cysteine, threonine (N‐terminalnucleophile hydrolases), aspartic, metallo‐, glutamic, and asparagine proteases (with thelatter two being found only in fungi or viruses) (Rawlings et al., 2010). The diversity ofproteases is further increased by the frequent attachment of auxiliary, non‐proteolyticdomains to the catalytic core (López‐Otín, Overall, 2002; Puente et al., 2003) providingprotease substrate specificity, guiding its cellular localization, modifying kinetic propertiesand sensitivity to endogenous inhibitors. According to evolutional protease classification –MEROPS (Rawlings, Barrett, 1993; Rawlings et al., 2010) – all proteases (192053 sequences,3895 identifiers to date) can be further divided into 226 families on the basis of aminoacidsequence comparison, and these families can be assembled into 57 clans on the basis of192