Hexokinase catalysis

Consider the case of glucose (Glc) and ATP interactions with hexokinase (HK) in the absence of catalysis (which can be accomplished by omitting magnesium ion). 

Although precise positioning of the reactants is a fundamental aspect of enzyme catalysis, most enzymes undergo some change in their structure when they bind substrates. A particularly dramatic example is hexokinase, which catalyzes the transfer of a phosphate group from adenosine triphosphate (ATP) to glucose. 

Structural studies of the oxy-Cope catalytic antibody system reinforce the idea that conformational dynamics of both protein and substrate are intimately intertwined with enzyme catalysis, and consideration of these dynamics is essential for complete understanding of biologically catalyzed reactions. Indeed, recent single molecule kinetic studies of enzyme-catalyzed reactions also suggest that different conformations of proteins are associated with different catalytic rates (Xie and Lu, 1999). In addition, a number of enzymes are known to undergo conformational changes on binding of substrate (Koshland, 1987) that lead to enhanced catalysis two examples are hexokinase (Anderson and Steitz, 1975 Dela-Fuente and Sols, 1970) and triosephosphate isomerase (Knowles, 1991). 

Numerous examples of this basic mechanism of catalysis can be found among the EC Class 2 enzymes. One example is hexokinase. 

Figure 16.3 Induced fit in hexokinase. As shown nn blue, the two lobes of hexokinase are separated in the absence of glucose. The conformation of hexokinase changes markedly on binding glucose, as shown in red. Notice that two lobes of the enzyme come together and surround the substrate, creating the necessary environment for catalysis.[Courtesy of Dr. Thomas Steitz.]...

We ll look at enzymes in more detail in Section 26.10, but you may already be aware that an enzyme is a large, globular, protein molecule that contains in its stmcture a protected pocket called its active site. The active site is lined by acidic or basic groups as needed for catalysis and has precisely the right shape to bind and hold a substrate molecule in the orientation necessary for reaction. Figure 6.9 shows a molecular model of hexokinase, along with an X-ray crystal stmcture of the glucose substrate and adenosine diphosphate (ADP) bound... 

Figure 6.9 Models of hexokinase in space filling and wire frame formats, showing the cleft that contains the active site where substrate binding and reaction catalysis occur. At the bottom is an X-ray crystal structure of the enzyme active site, showing the positions of both glucose and ADP as well as a lysine amino acid that acts as a base to deprotonate glucose.

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