Factor active site substrate sequences

Initial efforts have concentrated on the functional aspects of enzymes, that is, their active sites. While nature has provided a wealth of enzymes with varying substrate activities, there exists a need for additional sources and types of enzymes with higher mmover rates and substrate specificities. This has resulted from the fact that many commercially valuable enzymes are, in economic terms at least, less efficient than desired, often needing co-factors as catalysts. Based on sequence structure ftinction data, site-directed mutagenesis has generated new variants with higher substrate binding affinities. 

The ability of proteins to do work on the molecules they bind depends upon several factors. The active sites of enzymes bring reactive groups on both the substrate and protein together. Active sites often contain acidic or basic groups that act as chemical catalysts. They may also distort the structure of the substrate to make it resemble the transition state of the reaction being catalyzed. The flexibility of protein structures is also important because it allows the bound molecule to go through a sequence of interactions with the protein. 

Redirecting reactions via conformational control In the final example of this chapter, we will show how understanding of enzyme stereoelectronics allows one to redirect reactivity of known substrate into a new direction. When the stractural constraints of enzyme active sites are removed, a new set of stereoelectronic constraints can be imposed on the same substrate to enforce a different reactivity. For example, the effect of stereoelectronic factors on the relative order of steps in the deprotonation/decarboxylation sequence were recently analyzed for an enzyme-catalyzed vs. Cu-catalyzed reactions of the similar substrates (Figure 11.66). The first process is involved in the biosynthesis of polyketides and fatty acids where enzymatic activation of... 

---