Boreskov

PP‐33similarities in their three‐dimensional folding. Variability of known and putative proteasesreflects the descent of modern proteins from a limited number of ancestral forms.The recent availability of the genome sequence of different organisms has allowed theidentification of their entire protease repertoire. The extensive biological and pathologicalimplications of this large set of proteins with a common biochemical function led to theconcept of proteases as a distinct subset of the proteome called degradome – the completeset of proteases present in an organism (López‐Otín, Overall, 2002). For example, the humandegradome consists of 569 active proteases, 175 putative proteases and pseudogenes, 410inactive homologues, accounting for 2% of structural genes in humans (Quesada et al., 2009).Many families of human proteases are also clearly recognizable in the genomes of D.melanogaster, C. elegans and A. thaliana. This indicates the existence of universalproteolytic routines in these organisms, although they are frequently expanded invertebrates. It has become evident that, in addition to highly conserved protein turnover,proteases are also precise posttranslational modifiers of important signaling molecules,including ligands, receptors, adaptors, kinases and transcription factors. Moreover,proteases modify and influence each other forming the protease web. Biological meaningfulof protease diversity (size, shape, specificity, optimal microenvironment, domainarchitecture, etc.) in the organisms of different taxa is on the centre of discussion with thespecial emphasis to protease family C2, or calpains.The work was supported by the projects of RFBR 11‐04‐00167, Ministry of Education &Science RF 14.740.11.1034, “Scientific Schools” 3731.2010.4, and “Bioresources”.References[1]. López‐Otín C., Bond J.S. Proteases: multifunctional enzymes in life and disease. J. Biol. Chem. 2008.283:30433‐7.[2]. López‐Otín C., Overall C.M. Protease degradomics: a new challenge for proteomics. Nat. Rev. Mol. Cell.Biol. 2002. 3:509‐19.[3]. Nemova N.N., Bondareva L.A. To the problem of proteolytic enzyme evolution. Biochemistry. Ser. BBiomed. Chem. 2008. 2:115‐25.[4]. Puente X.S., Sánchez L.M., Overall C.M., López‐Otín C. Human and mouse proteases: a comparativegenomic approach. Nature Rev. Genet. 2003. 4:545‐58.[5]. Quesada V., Ordóñez G.R., Sánchez L.M., Puente X.S., López‐Otín C. The Degradome database: mammalianproteases and diseases of proteolysis. Nucl. Acids Res. 2009. 37:D239‐43.[6]. Rawlings N.D., Barrett A.J. Evolutionary families of peptidases. Biochem J. 1993. 290(Pt 1):205‐18.[7]. Rawlings N.D., Barrett A.J., Bateman A. MEROPS: the peptidase database. Nucl. Acids Res. 2010. 38:D227‐33.[8]. Seife C. Blunting nature's Swiss army knife [news]. Science. 1997. 277:1602‐3.[9]. Turk B. Targeting proteases: successes, failures and future prospects. Nat. Rev. Drug Discov. 2006, 5:785‐99.193