Glutamine and residues

By the use of a model system, Kimura et al. [17] tried to mimic the function of the two mechanistically most typical zinc(II) enzymes. Carbonic anhydrase (CA, EC 4.2.1.1) catalyses the reversible hydration of carbon dioxide to bicarbonate ion and its zinc(II) active site is bound to three histidine residues and a water molecule. Carboxypeptidase A (CPA, EC 3.4.17.1) catalyses the hydrolysis of the hydrophobic C-terminal amino acids from polypeptides, and its active-site zinc(II) is bound to two histidine residues, a glutamine residue and a water molecule which is hydrogen bound to a glutamine residue (Scheme 19). 

Transglutaminase Transfer of acyl groups between the y-carboxyamide group of peptide-bound glutamine residues and various amines, including the -amino group of peptide-bound lysine, to form intra- and inter-molecular e-(y-glutamyl)lysine... 

Figure 29.31. Structure of a Release Factor. The structure of a eukaryotic release factor reveals atRNA-like fold. The acceptor-stem mimic includes the sequence Gly-Gly-Gln at its tip. This region appears to bind a water molecule, which may be brought into the peptidyl transferase center. There it can participate in the cleavage of the peptidyl-tRNA ester bond, with the aid of the glutamine residue and the ribosomal catalytic apparatus. 

The general approach for carboxyl protection is esterification. The simplest solution, the use of methyl or ethyl esters, is suitable for semipermanent blocking, although the commonly applied process of unmasking, alkaline hydrolysis, is far from unequivocal. It is accompanied by racemization, partial hydrolysis of carboxamide groups in the side chain of asparagine and glutamine residues and by several other side reactions which are initiated by proton abstraction (Cf. Chapter VII). Nevertheless, perhaps because of the attractively simple esterification of amino acids... 

Ironically, while water is critical in maintaining molecular shape, the aqueous state is not one in which proteins are long resistant to denaturation. A variety of environmental changes such as temperature, pH, salts and solvents can cause protein inactivation in the aqueous state, and the mechanisms of irreversible protein inactivation often follow conunon pathways. These include cystein destruction, thiol-catalyzed disulfide interchange, oxidation of cystein residues, deamidation of asparagine and glutamine residues and hydrolysis of peptide bonds at aspartic acid residues. 

The enzymes used to create ELP hydrogels in a biocompatible process is transglutaminase (tTG] (Bozzini etal., 2011]. The enzyme catalyzes the calcium-dependent acyl transfer reaction that results in the formation of a y-glutamyl- -lysyl covalent bond between peptide-bound glutamine residues and various primary amines. 

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