Protein, amino acid turnover hydrolysis

Water, however, carries both nucleophilic and electrophilic centers. This means that water reacts with many biomolecules in a way that damages them. In the case of proteins, as noted above, water reacts with the amide backbone to degrade proteins, generating amino acids as hydrolysis products (see Figure 2.13). This can be disadvantageous if the protein is desired, as it requires that the protein be re-synthesized. The turnover of proteins is important, however, in any system living in a dynamic environment. Thus, the hydrolytic instability of proteins in water is key to maintaining life. 

Baltzer s group has recently described a fully-synthetic protein that is also capable of hydrolysing p-nitrophenyl esters the polypeptide, which contains 42 amino acids, was designed to fold into a hairpin helix-loop-helix motif that dimerises into a four-helix bundle. The dimer is predicted to present on its surface a shallow reactive site containing several histidine residues. The spectroscopic properties of the peptide are consistent with the predicted folded structure, and the molecule does indeed catalyse ester hydrolysis (and transesterification) more effectively than 4-methylimidazole does. However, there is little substrate selectivity, and not much turnover. The histidine array does not seem to act via general acid-base catalysis, but rather to bind and stabilise ester oxygens in the transition state. We return to this molecule below. 

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