Introduction to Enzymes
Part IV
Part IV. The Active Site of the Enzyme.
Each enzyme has a unique active site.
Active site = catalytic site.
The enzyme binds its substrate(s) at the active site and the enzyme catalyzes chemical changes in the substrate(s). The types of chemical reactions catalyzed were illustrated above in Fig. 4. The binding of a substrate (NAD+) to the active site of an enzyme is illustrated below:
Figure 5. NAD+ bound in the active site of GAP dehydrogenase. The NAD+ molecule is shown in bold and the side chains of the amino acids binding it are shown projecting from the surface of the enzyme (shown as the filled in area surrounding the active site).
Figure from Nature 266: 332 (1977).
Enzymes contain a large number of amino acids, but most AA side chains are used for forming the enzyme's shape. Only a few AA side chains are at the active site.
These special AA side chains:
1. Bind the substrate(s) and
2. Catalyze the reaction
This concept is illustrated in the following figures by 3 different drawings of the enzyme ribonuclease which catalyzes the hydrolysis of RNA. The first view is of the 3-D shape of the enzyme with the 3 key amino acids at the active site highlighted (His12, Lys41 and His119 - numbers indicating the position of these residues in the amino acid sequence of ribonuclease). Next is a ribbon model with the 3 key amino acids shown in relation to the various secondary structure elements of ribonuclease. Last is a ball-and-stick model of ribonuclease with the same 3 amino acid side chains of the active site emphasized. A freature to try to see in these models is the groove of the enzyme which forms the active site and how the enzyme folds to bring these 3 key amino acid side chains together to form the active site.
Figure 6. 3-D model of the enzyme ribonuclease with the key amino acid side chains at the active site shown in red. The active site is a deep groove at the center of this structure.
Figure 7. Ribbon model of ribonuclease which emphasizes the secondary structure of the enzyme. The key amino acid side chains are shown projecting into the active site groove. The dashed line indicates a section of the polypeptide backbone removed by proteolysis during processing of the enzyme in the intestine where it functions.
Figure 8. Ball-and-stick model of ribonuclease with the side chains of the 3 key amino acids in the active site groove shown in bold. Compare this model to the ribbon model above.
These figures are from Zubay et al., Principles of Biochemsitry copyright ©1995 Brown Comm.
Summary of the Active Site of Enzymes:
1. Enzyme has large structure with hundreds of AA side chains but only a few are involved in catalysis.
2. Each enzyme has a unique active site.
3. Key AA side chains are involved in binding and catalysis in the active site.
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©Wilbur H. Campbell, 1995; wcampbel@mtu.edu