Protein function evolution proteases

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. 

These criteria are in descending order of strength. If criteria 1 and 2 hold, the rest will follow, in most—but not all—cases. Note that in the serine proteases, tertiary structure is more conserved than primary structure. Sometimes structure has been conserved through evolution, but function has changed that is, criteria 3 and 4 do not hold. For example, the binding protein haptoglobin appears to have diverged from the serine proteases. 

While a few very potent non-peptide protease inhibitors (Pis) have been isolated from plants many plant protease inhibitor proteins (PIPs) have evolved to have protease interaction Kj values in the nanomolar and picomolar range. These extraordinary affinities derive from the matching of the PI protein amino sequence about the scissile peptide bond (Pl-Pl ) and evolution of adjacent sequences to fit and interact appropriately within the target protease active site [1, 120, 121]. The structure and function of the different classes of PI proteins from plants are succinctly but comprehensively reviewed below. 

Structure analysis of several proteases involved in blood coagulation and fibrinolysis reveals a diverse, sometimes repetitive, assembly of discrete protein modules (Fig. 9.4) [56]. While these modules represent independent structural units with individual folding pathways, their concerted action contributes to function and specificity in the final protein product. On the genetic level, these individual modules are encoded in separate exons. Over the course of modular protein evolution, new genes are created by duplication, deletion, and rearrangement of these exons. Mechanistically, the exon shuffling actually takes place in the intervening intron sequences (intronic recombination - for further details see [10]). 

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