Proteases probably arose at the earliest stages of protein evolution as simple destructive enzymes essential for protein catabolism and the production of amino acids in primal organisms.
For many years, researches on proteases focused on their original roles as blunt aggressors related with protein destruction. However, the realization that, outside these nonspecific degradative functions, proteases act as razor-sharp scissors and catalyze highly explicit reactions of proteolytic processing, generating new protein products, inaugurated a new phase in protease research.
The present success of research in this group of primitive enzymes derives primarily from the big collection of findings showing their relevance in controlling multiple biological processes in all living species. Thus, proteases regulate the outcome, localization, and actions of many proteins, modulate protein-protein interactions, produce new bioactive molecules, add to the processing of cellular information, and transduce, produce, and intensify molecular signals.
As a direct outcome of these multiple activities, proteases influence DNA transcription and replication, cell proliferation and differentiation, heat shock and unfolded protein responses, tissue morphogenesis and remodeling, neurogenesis, ovulation, angiogenesis, fertilization, stem cell mobilization, wound repair, hemostasis, inflammation, blood coagulation, autophagy, immunity, senescence, apoptosis and necrosis.
Consistent with these necessary roles of proteases in cell survival and behavior and death of all organisms, alterations in proteolytic systems underlie multiple pathological conditions such as neurodegenerative disorders, cancer, and inflammation & cardiovascular diseases.
Accordingly, many proteases are giving attention to the pharmaceutical industry as potential drug targets or as diagnostic and prognostic biomarkers. Proteases also play key roles in plants and contribute to the maturation, processing, or destruction of specific proteins in response to developmental cues or to changes in environmental conditions. Likewise, many infectious microorganisms need proteases to replicate or use proteases as virulence factors, which have facilitated the development of protease-related therapies for diseases of enormous relevance to human life for example AIDS. Finally, proteases are also vital tools of the biotechnological industry for their usefulness as biochemical reagents or in the manufacture of various products.
This outstanding range in protease functions directly results from the evolutionary creation of a multiplicity of enzymes that show a number of shapes and sizes. Thus, the architectural design of proteases varies from tiny enzymes made up of simple catalytic units (∼20 kDa) to refined protein-processing and degradation machines, like the proteasome and meprin metalloproteinase isoforms (0.7–6 MDa).
In terms of specificity, variety is also a common law. Thus, some proteases show a delicate specificity toward a distinctive peptide bond of a single protein (e.g. angiotensin-converting enzyme); however, most proteases are comparatively nonspecific for substrates, and some are obviously promiscuous and aim multiple substrates in a random manner (e.g. proteinase K). Proteases also follow different approaches to establish their appropriate position in the cellular geography and, in most instances, operate in the context of complex networks consisting distinct proteases, cofactors, substrates, inhibitors, receptors, adaptors, and binding proteins, which provide an extra level of interest but also complexity to the research of proteolytic enzymes.