Serine functional group

All the well-characterized proteinases belong to one or other of four families serine, cysteine, aspartic, or metallo proteinases. This classification is based on a functional criterion, namely, the nature of the most prominent functional group in the active site. Members of the same functional family are usually evolutionarily related, but there are exceptions to this rule. We... 

As an alternative to peptidic inhibitors, which display electrostatic interactions with the active site, covalent inhibitors have also been described recently. Such peptides bear a functional group that can react reversibly with the catalytic serine of the protease. These include aldehydes, a-ketoacid derivates, lactams and boronates. 

The functional groups of the enzyme involved in the chemical bonding are the TV-terminal and s-amino groups (from lysine) as well as the carboxy-(aspartic or glutamic acid), sulfhydryl- (cysteine), hydroxyl- (serine, threonine), indole (tryptophan), imidazole (hystidine) and phenolic (tyrosine) functions. 

FIGURE 3.10 Deprotection of functional groups by beta-elimination.17 (A) Removal of a labile proton beta to a good leaving group leads to release of the protector as the didehydro compound. (B) Recently developed protectors (Samukov et al., 1988) also designated untra-ditionally as 4-nitrophenyl- (C) Transformation of an O-protected serine residue into a dehydroalanine residue by hefa-elimination. 

Only three amino acids have a hydroxyl functional group in their side chain tyrosine, serine and threonine. Some kinases target only tyrosine residues (tyrosine kinases) whereas others may phosphorylate serine or threonine (Ser/Thr kinases). An enzyme protein (the substrate for the kinase) may have several tyrosine, serine or threonine residues within its primary sequence, but only some of these are subject to phosphorylation by a particular kinase (see Figure 3.6)... 

These three catalytic functionalities are similar in practically all hydrolytic enzymes, but the actual functional groups performing the reactions differ among hydrolases. Based on the structures of their catalytic sites, hydrolases can be divided into five classes, namely serine hydrolases, threonine hydrolases, cysteine hydrolases, aspartic hydrolases, and metallohydrolases, to which the similarly acting calcium-dependent hydrolases can be added. Hydrolases of yet unknown catalytic mechanism also exist. 

Classincation of the Proteases. The classification of the proteases is based on their mechanism of catalysis (4), The four primary classes of proteases are the serine, aspartic, cysteine, and metalloproteases (5). This classification is based on the primary functional group found in the en me s active site. There are likely to be other proteases eventually characterized which will not precisely fit into this categorization scheme and additional categories will be needed. One example of a potential new category is the ATP-dependent proteinases (6), a group of proteinases which require ATP for activity. 

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. 

Amino acids have been used in ex-chiral-pool syntheses far less frequently. The most popular starting material is serine (available in both configurations), due to the differentiable functional groups at the termini. L-Serine (1) may be converted into a variety of (R)-amino acids 5 by straightforward manipulations12. 

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