Enzyme

Protein structural studies are a very active area of biochemical research, and it is known that the biological function (activity) of an enzyme is related to its structure. There are 20 common amino acids which make up the building blocks of all known enzymes. They have similar structures, differing mainly in their substituents. The organic substituent of an amino acid is called the R group. The structure of the amino acid alanine is depicted in Figure 1.

The biologically common amino acids are designated as L-amino acids because the amino group is on the left of the a alpha-carbon when the molecule is drawn as indicated. This is called Fischer projection. The amino acids are covalently joined via peptide bonds. A series of three amino acids is shown in Figure 2, illustrating the structure of a tripeptide. Enzymes have many peptide linkages and range in molecular mass from 12,000 to greater than one million.

Enzymes may also consist of more than a single polypeptide chain. Each polypeptide chain is called a subunit, and may have a separate catalytic function. Some enzymes have non-protein groups which are necessary for enzymatic activity. Metal ions and organic molecules called coenzymes are components of many enzymes. Coenzymes which are tightly or covalently attached to enzymes are termed prosthetic groups. Prosthetic groups contain critical chemical groups which allow the overall catalytic event to occur.

Enzymes bind their reactants (substrates) at special folds and clefts in their structures called "active sites." Because active sites have chemical groups precisely located and orientated for binding the substrate, they generally display a high degree of substrate specificity. The active site of an enzyme consists of two key regions. The Figure 2. Illustration by Hans & Cassidy. Courtesy of Gale Group. catalytic site, which interacts with the substrate during the reaction, and the binding site, the chemical groups of the enzyme which bind the substrate to allow chemical interaction at the catalytic site.

Although the details of enzyme active sites differ between different enzymes, there are common motifs. The active site represents only a small fraction of the total protein volume. The reason enzymes are so large is that many interactions are necessary for reaction. The crevice of the active site creates a microenvironment which is critical for catalysis. Environmental factors include polarity, hydrophobicity, and precise arrangement of atoms and chemical groups. In 1890 Emil Fischer compared the enzyme-substrate relationship to a "lockand-key." Fischer postulated that the active site and the enzyme have complimentary three dimensional shapes. This model was extended by Daniel Koshland Jr. in 1958 by his "induced fit" model, which reasoned that actives sites are complimentary to substrate shape only after the substrate is bound (Fig. 3).