Regulatory Enzymes

Abstract

The history of regulatory enzymes has its roots in the history of enzymes in general. The theoretical framework of how enzymes work was founded by Emil Fischer in 1894. Fischer discovered that some enzymes can distinguish between two closely related substrates, such as two stereoisomeric sugars. On this basis he formulated the “lock and key” model which hypothesizes that enzymes have specific sites that can accommodate ligands which have a complementary structure. The lock and key model is based on the existence of a geometrical fit between the substrate (the key) and the binding site (the lock); see Fig. 8.1a. This model has undergone several modifications and generalizations. The first modification follows from the recognition that a geometrical fit does not necessarily imply the strongest affinity between the enzyme and the ligand. The more important quantity is the binding free energy. To achieve the largest (in absolute magnitude) binding free energy, one does not need to have a geometrical fit. A complementary pattern of functional groups (such as charged, hydrogen-bonding, and hydrophobic groups) can produce a strong affinity between the ligand and the site even without a geometrical complementarity (Fig. 8.1b). In fact, one can show that solvent effects can produce strong affinity even when there is neither a geometrical nor a complementary pattern fit (Fig. 8.1c). In this case, the possibility of the formation of hydrogen-bonded bridges by solvent molecules is the main driving force for selecting the binding site (see also Chapter 9).