Lock-and-key fit

Enzymes are large proteins that function as biological catalysts and whose specificity is due to a lock-and-key fit between enzyme and substrate. Enzymes contain a crevice, inside which is an active site, a small three-dimensional region of the enzyme with the specific shape necessary to bind the proper substrate. 

The study of these biogenetic pathways was much assisted by the use of isotopic labeling, and Harold Urey (1893-1987) at Columbia and Martin D. Kamen (b.1913) at Berkeley were both proto-bioorganic chemists. In more recent years, NMR has come to play an important role in both mechanism and structure studies (see section on physical instrumentation). The concept of a relationship between the structure of a compound and its biochemical functioning goes back to Emil Fischer s model of a lock and key , first formulated in 1894, but many years were to elapse before bioorganic chemists were able to show how the lock and key fitted together. 

A schematic diagram of the reaction of an enzyme with a substrate, indicating their relative sizes (typically about 10 nm for a medium-sized enzyme and 0.1—1.0 nm for the substrate) and the lock and key fit. 

Binding of small antigens, e.g., haptens, to antibodies occurs when hypervariable region amino acid residues form a pocket into which the hapten fits. Such binding is similar to that between enzymes and small-molecule substrates, i.e., a lock-and-key fit between antigen and... 

In eq 6, K is the Michaelis constant. Good correlation with a was also obtained with V. The best linear relations with a have been found using more or less pure enzjraies. The lack of success with a in biochemical systems has generally been attributed to steric interactions of substituents with the enzyme or lipoprotein membranes. Recent work would Indicate that while steric interactions are extremely important, the concept of lock-and-key fit of enzyme and substrate has been over-emphasized at the expense of hydrophobic bonding. The importance to the medicinal. chemist of the more flexible character of enzymes which is emerging from the work of Koshland and others has been analyzed by Belleau . ... 

Molecular complementarity is the lock-and-key fit between molecules whose shapes, charges, and other physical properties are complementary. Multiple noncovalent interactions can form between complementary molecules, causing them to bind tightly (see Figure 2-10), but not between molecules that are not complementary. 

This type of lock-and-key fit between the active site of a protein and a particular molecule is important not only to taste but to many other biological functions as well. For example, immune response, the sense of smell, and many types of drug action all depend on shape-specific interactions between molecules and proteins. The ability of scientists to determine the shapes of key biological molecules is largely responsible for the revolution in biology that has occurred over the last 50 years. 

The concept of constrained geometry is also important and this is why 7i-complexes of metal and olefins can lead to structured molecules. For example a model of cyclododecatriene-nickel shows that the nickel atom is situated exactly in the center of the ring. This picture represents a lock and key fit very precisely another analogy with an enzyme-substrate complex. 

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