Acid proteases evolution

Figure 4, Proposed scheme for the evolution of acid proteases...

The mammalian serine proteases appear to represent a classic case of divergent evolution. All were presumably derived from a common ancestral serine protease.23 Proteins derived from a common ancestor are said to be homologous. Some nonmammalian serine proteases are 20 to 50% identical in sequence with their mammalian counterparts. The crystal structure of the elastase-like protease from Streptomyces griseus has two-thirds of the residues in a conformation similar to those in the mammalian enzymes, despite having only 186 amino acids in its sequence, compared with 245 in a-chymotrypsin. The bacterial enzymes and the pancreatic ones have probably evolved from a common precursor. 

Deamer [121] and others have advocated peptide evolution in early protocells capable of energy-transduction. He suggests the first membranes may have been made of monocarboxylic acids and alcohol. However, peptide evolution in protocells lacks any plausible mechanism for heredity of sequence. New sequences (e.g. coding for ligases or proteases) would have to be rediscovered in each lifetime. 

Mirror-Image Proteins As noted in Chapter 3, The amino acid residues in protein molecules are exclusively L stereoisomers. It is not clear whether this selectivity is necessary for proper protein function or is an accident of evolution. To explore this question, Milton and colleagues (1992) published a study of an enzyme made entirely of D stereoisomers. The enzyme they chose was HIV protease, a proteolytic enzyme made by HIV that converts inactive viral pre-proteins to their active forms. 

The charge relay system is found at the active site of a group of enzymes called serine proteases. They include chymotrypsin, trypsin, a-lytic protease, elastase, and subtilisin. It is interesting that the charge relay system was found in enzymes belonging to different branches of diemical evolution (chymotrypsin and subtilisin). This suggests that this system is a hydrolytic catalytic system of general importance which is derived solely from amino acid residues. 

Directed evolution has also been very effective for increasing enzyme activity in organic solvents 14> For example, the serine protease subtilisin can catalyze specific peptide syntheses and transesterification reactions, but organic solvents are required to drive the reaction towards synthesis. Sequential rounds of error-prone PCR and visual screening yielded a subtilisin variant with twelve amino acid substitutions that was 471 times more active than wild-type in 60% dimethylforma-mide (DMF)[145- 22° this enzyme is much more effective for peptide and polymer synthesis. 

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