Bridging phases in high-response piezoelectric materials

Abstract

Proteolytic activity is important for normal functioning of an organism andmust be rigorously controlled due to its potential danger. Failure in biological control mechanisms of proteolytic activities may result in a disease. Emerging biological roles of lysosomal cysteine proteases are bringing them in the focus of drug discovery research. They are expressed in variety of organisms frombacteria to humans (for the group ofmammalian homologues the term cysteine cathepsins is used). Cysteine cathepsins are lysosomal proteases involved in processing and digestion. These enzymes have rather short active site cleft, comprising of only three well defined substrate binding subsites (S2, S1 and S1’) and rather broad binding areas (S4, S3, S2’, S3’), which makes them distinct from other protease classes such as serine and aspartic with six and eight substrate binding sites, respectively. There are eleven human enzymes currently known (cathepsins B, C, F, H, L, K, O, S, V, X andW). Exopeptidases (cathepsins B, C, H, X), in contrast to endopeptidases (such as cathepsins L, S, V and F), provide features, which facilitate binding of Nand Cterminal groups of substrates in the active site cleft. Besides clear preference for free chain termini in the case of exopeptidases, the substrate binding sites exhibit no strict specificity. Their subsite specificity is rather exclusive than limiting. Our study of their interactions with protein inhibitors addresses their roles in the endosomal pathway of the immune system response. During this process foreign proteins are degraded to peptides of appropriate length, which must be delivered at the moment when the last piece of invariant chain (CLIP peptide) leaves the binding groove of the MHC class II molecules andmakes it available for peptide binding and antigen presentation. P12