Protease highly specific

The most widely used of these types are the proteases, but the others may be useful in some circumstances. A characteristic feature is that individual enzymes are highly specific in their action, so that although one protease may yield the required effect, another may fail to do so. 

Crixivan interacts in a highly specific way with the three-dimensional structure of HIV protease. 

Mesoporous silicas have characteristics of high specific surface areas and pores with defined dimensions and uniform distribution. These features make mesoporous systems ideal candidates as host materials to guest bio-molecules. Protein stability may be enhanced due to reduced autolysis in the case of protease enzymes, and more generally reduced protein aggregation, as a result of the separation of the molecules adsorbed on the surface. 

Proteases (endopeptidases or proteinases) commonly used for specific cleavage of proteins are summarised in Table 6.2. Trypsin is almost always used as an enzyme of first choice it is highly specific and stable, has an appropriate pH-optimum and is commercially available in high purity and quality. When the results obtained are ambiguous, or the trypsin cannot be used for any other reason, a different protease can be easily chosen. In all experiments, described here, the trypsin cleavage was applied. 

Whereas standard proteases use serine, cysteine, aspartate, or metals to cleave peptide bonds, the proteasome employs an unusual catalytic mechanism. N-terminal threonine residues are generated by self-removal of short peptide extensions from the active yS-subunits and act as nucleophiles during peptide-bond hydrolysis [23]. Given its unusual catalytic mechanism, it is not surprising that there are highly specific inhibitors of the proteasome. The fungal metabolite lactacystin and the bacterial product epoxomicin covalently modify the active-site threonines and in-... 

Substrate Analog Inhibitors of Highly Specific Proteases... 

Highly specific proteolytic enzymes cleave a single peptide bond in a naturally occurring substrate. These proteases appear to be Integral parts of many biologic processes and may be contrasted with less specific proteases Isolated from the gastrointestinal tract. 

Highly specific proteases appear to cleave substrates by the same mechanisms used by more general proteases. Serine proteases, metaloproteases, and aspartyl proteases with greatly restricted specificity have been Identified. Specificity appears to reside in the Eirchitecture of the active site rather than in functional groups which hydrolyze the peptide bond. 

The use of substrate analogs has led to the rapid development of inhibitors for several highly specific proteases. Research from this laboratory on the development of renin Inhibitors, kalllkreln Inhibitors, and Inhibitors of IgA-) protease Is outlined below. 

The complex of SNAREs and SNAP25 is the target of the powerful Clostridium, botulinum, toxin, a protease that cleaves specific bonds in these proteins, preventing neurotransmission and causing the death of the organism. Because of its very high specificity for these proteins, purified botulinum toxin has served as a powerful tool for dissecting the mechanism of neurotransmitter release in vivo and in vitro. 

The intense interest in y - am i n o - (i -hydroxy acid related peptides has led to a great deal of effort devoted to their synthesis. Statine analogues Ahppa (11), Achpa (12), and Dahoa (13) (Scheme 2), which correspond to the replacement of the chain equivalent of leucine in statine by those of phenylalanine, cyclohexylalanine, and lysine, respectively, were used to synthesize inhibitors of pepsin, renin, and penicillinopepsinJ1314] With the objective of developing highly specific inhibitors, C2-substituted analogues have also been introduced into short, substrate-derived inhibitors, e.g. the a,a-difluoro statine 14 in renin inhibitors,1151 and N -substituted statine derivatives like 15 in HIV-1 protease inhibitors.[16]... 

The first pyrolysin to be cloned from a higher plant was cucumisin from Cucumis melo, an extracellular protease highly abundant in melon fruit [152], Cucumisin was shown to have a broad substrate specificity in that it cleaves a variety of small peptide substrates and eight peptide bonds within the oxidized insulin B chain [153-155]. A similar, broad... 

The separation of the target protein from the fusion protein can be performed chemically or enzymatically. The basis for chemical cleavage is acid or base stability of the target protein. Enzymatic separation by proteases is highly specific but its efficiency can be decreased by limited access to the part of the amino acid sequence required for proteolysis. 

Fourth, the demonstration that many of these enzymes have prognostic value in cancer may qualify them as novel therapeutic targets. For example, similar to many other proteases, these enzymes may participate in the digestion of extracellular matrix, thus facilitating tumor invasion and metastasis. The identification of highly specific inhibitors may reveal new therapeutic opportunities. 

The L chains of BoNTs and TeNT are highly specific proteases that recognize and cleave only three proteins, the so-called SNARE proteins, which form the core of the neuroexocytosis apparatus (Figure 4) (Schiavo et al. 2000). TeNT, BoNT/B, /D, /F and /G cleave VAMP, a protein of the SV membrane, at different single peptide... 

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