Peptidase

The main LAB endopeptidases that have been characterized are PepO, PepF, PepG, and PepE, all of which act on NHj-X fX -COOH substrates. PepO is encoded by three paralogous genes ipepO, 

Dipeptidases are exopeptidases specific forNH2-XiX-COOH dipeptides. The PepD dipeptidase family has a broad specificity for various dipeptides. The pepD genes are distributed heterogeneously in LAB genomes and can vary in number from 0 to 6 paralogs. PepV is also encoded by multiple paralogous genes. It is present in all LAB and also has a broad specificity. 

Tripeptidases release the amino acid from the iV-terminal position of NH2-XiX-X-COOH tripeptides. They have a broad specificity but preferentially target hydrophobic peptides and do not hydrolyze proline residues. The only tripeptidase currently identified in LAB is PepT. The pepTgene is present in all LAB genomes and can occur as two paralogous genes in some LAB (Lact. acidophilus, Lact. johnsonii, and Lactobacillus gasseri). 

Proline-specific peptidases can hydrolyze proUne residues from the A-terminal position of peptides. Proline iminopeptidase (PepI) has aminopeptidase activity towards A-terminal proline peptides and prefers tri-peptides (NH2-Pro, Xn-COOH). The prolinase PepR has a broad specificity for dipeptides (NH2-ProiX-COOH). These proline-specific peptidases are absent from all L. lactis strains. The activity of cell extract fi-om Lact. helveticus and Lact. rhamnosus for several proline dipeptides was significantly reduced in PepR-deletion mutant. Those observations suggest that PepI and PepR may contribute to the specific proteolytic capacity for breaking down peptides containing proline in Lactobacillus strains (Liu et al. 2010). 

In the dairy industry the formation of casein curd is achieved with chymosin or rennin (cf. Table 2.20) by a reaction mechanism described under section 10.1.2.1.1. Casein is also precipitated through the action of other proteinases by a mechanism which involves secondary proteo- 

Plant proteinases (cf. Table 2.22) and also those of microorganisms are utilized for ripening and tenderizing meat. The practical problem to be solved is how to achieve uniform distribution of the enzymes in muscle tissue. An optional method appears to be injection of the proteinase into the blood stream immediately before slaughter, or rehydration of the freeze-dried meat in enzyme solutions. 

Cold turbidity in beer is associated with protein sedimentation. This can be eliminated by hydrolysis of protein using plant proteinases (cf. Table 2.22). Utilization of papain was suggested by Wallerstein in 1911. Production of conplete or partial protein hydrolysates by enzymatic methods is another example of an industrial use of proteinases. This is used in the liquefaction of fish proteins to make products with good flavors. 

Amylases are either produced by bacteria or yeasts (Table 2.20) or they belong to the components of malt preparations. The high temperature-resistant bacterial amylases, particularly those of Bac. licheniformis (Fig. 2.49) are of interest for the hydrolysis of corn starch (gelatinization at 105-110 °C). The hydrolysis rate of these enzymes can be enhanced further 

Name Source pH optimum Optimal stability pH range 

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Hydrolases. Enzymes catalysing the hydrolytic cleavage ofC —O, C —N and C —C bonds. The systematic name always includes hydrolase but the recommended name is often formed by the addition of ase to the substrate. Examples are esterases, glucosidases, peptidases, proteinases, phospholipases. Other bonds may be cleaved besides those cited, e.g. during the action of sulphatases and phosphatases. 

Polypeptide hormones are synthesized as part of a larger precursor molecule or prohormone. Cleavage of the prohormone by specific cellular enzymes, ie, peptidases, produces the secreted form of the hormone. In some cases, multiple bioactive hormones are produced from a single prohormone. 

Metabolic Functions. Zinc is essential for the function of many enzymes, either in the active site, ie, as a nondialyzable component, of numerous metahoenzymes or as a dialyzable activator in various other enzyme systems (91,92). WeU-characterized zinc metahoenzymes are the carboxypeptidases A and B, thermolysin, neutral protease, leucine amino peptidase, carbonic anhydrase, alkaline phosphatase, aldolase (yeast), alcohol... 

Table 4. Neural Endopeptidase (Atrial Peptidase) Inhibitors...

Figure 4.20 Detailed view of the zinc environment in carboxy-peptidase. The active-site zinc atom is bound to His 69 and Glu 72, which are part of the loop region outside P strand 2. In addition, His 196, which is the last residue of P strand 5, also binds the zinc.

Several drugs in current medical use are mechanism-based enzyme inactivators. Eor example, the antibiotic penicillin exerts its effects by covalently reacting with an essential serine residue in the active site of glycoprotein peptidase, an enzyme that acts to cross-link the peptidoglycan chains during synthesis of bacterial cell walls (Eigure 14.17). Once cell wall synthesis is blocked, the bacterial cells are very susceptible to rupture by osmotic lysis, and bacterial growth is halted. 

Design, synthesis and evaluation of azapeptides, oxapeptides and related heterocycles as inhibitors of D,D-peptidase and (3-lactamase 95F455. 

It has been shown that glyeine amides of aminobenzophenones are readily converted to the corresponding benzodiazepines in vivo. Peptides which terminate in such a moiety should thus serve as a benzodiazepine prodrug after hydrolysis by peptidases. One of the glycine residues in lorzafone (194)is presumably removed metabolicaUy in this manner to give a benzodiazepine precursor which spontaneously cyclizes. Acylation of benzophenone 190 with the trityl protected dipeptide 191, as its acid chloride 192, affords the amide 193. Removal of the trityl protecting group with acid yields lorzafone (194) [50]. 

The incretin effect is reduced in type 2 diabetes, and this is attributed, at least in part, to reduced secretion of GLP-1. The biological actions of GLP-1 remain essentially intact in type 2 diabetes, but administration of extra GLP-1 is not a practical therapeutic option because the peptide is degraded rapidly if A < 2 min) by the enzyme dipeptidyl peptidase IV (DPP-4). DPP-4 cleaves the N-terminal dipeptide from many of the peptides that have either an alanine or a proline residue penultimate to the N-terminus (Fig. 6). 

DPP-1V inhibitors Inhibition of the dipeptidyl peptidase IV (by sitagliptin or vildagliptin) prolongs the duration of action of endogenous GLP-1 and thereby... 

An exopeptidase that sequentially releases a dipeptide from the N-terminus of a protein or peptide. Dipeptidy 1-peptidases are included in Enzyme Nomenclature subsubclass 3.4.14 along with tripeptidyl-peptidases. 

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