Secondary Forces Are Necessarily Are Basis By Which Enzyme

figure 3-11 Examples of van der Waals (hydrophobic) bonds between the nonpolar side groups of amino acids. The hydrogens are not indicated individually. For the sake of clarity, the van der Waals radii are reduced by 20%. The structural formulas adjacent to each space-filling drawing indicate the anangement of the atoms (a) Phenylalanine leucine bond, (b) Phenylalanine-phenylalanine bond (Sourte Adapted from Scheraga HA, The proteins, 2nd edition, p. 527 Copyright © Harold Scheraga. Used with permission )

third molecule that has a surface complementary to alanine. A methyl group is present in alanine but not in glycine. When alanine is bound to the third molecule, the van der Waals contacts around the methyl group yield 1 kcal/mol of energy, which is not released when glycine is hound instead. From Equation 3-4, we know lhat this small energy difference alone would give only a factor of 6 between the binding of alanine and glycine. However, this calculation does not take into consideration the fact that water is trying to exclude alanine much more than glycine. The presence of alanine's CHa group upsets the water lattice much more seriously than does the hydrogen alorn side group of glycine. At present, it is still difficult to predict how large a correction factor must be introduced for this disruption of the water lattice by the hydrophobic side groups. It is likely that the water tends to exclude alanine, thrusting it toward a third molecule, with a hydrophobic force of approximately 2 to 3 kcal/mol larger than the forces excluding glycine.

We thus arrive at the important conclusion that the energy difference between the binding of even the most similar molecules to a third molecule Iwhen the difference between the similar molecules involves a nonpolar group) is at least 2 to 3 kcal/mol greater in the aqueous interior of cells lhan under nonaqueous conditions. Frequently, the energy difference is 3 to 4 kcal/mol, since the molecules involved often contain polar groups that can form hydrogen bonds.

The Advantage of AQ between 2 and 5 kcal/mol

We have seen that the energy of just one secondary bond (2 to 5 kcal/mol) is often sufficient to ensure that a molecule preferentially binds to a selected group of molecules. Moreover, these energy differences are not so large that rigid lattice arrangements develop within a cell; that is, the interior of a cell never crystallizes, as it would if the energy of secondary bonds were several times greater. Larger energy differences would mean that the secondary bonds seldom break, resulting in low diffusion rates incompatible with cellular existence.

Weak Bonds Attach Enzymes to Substrates

Secondary forces are necessarily the basis by which enzymes and their substrates initially combine with each other. Enzymes do not indiscriminately bind all molecules, having noticeable affinity only for their own substrates.

Since enzymes catalyze both directions of a chemical reaction, they must have specific affinities for both sets of reacting molecules. In some cases, it is possible to measure an equilibrium constant for ¡he binding of an enzyme to one of its substrates (Equation 3-4), which consequently enables us to calculate the AC upon binding. This calculation in turn hints at which types of bonds may he involved. For AG values between 5 and 10 kcal/mol, several strong secondary bonds are the basis of specific enzymf;-suhstrale interactions. Also worth noting is that the AG of binding is never exceptionally high; thus, enzyme-substrate complexes can he both made and broken apart rapidly as a result of random thermal movement. This explains why enzymes can function quickly, sometimes as often as ID6 times per second. If enzymes were bound to their substrates, or more importantly to their products, by more powerful bonds, they would act much more slowly.

Weak Bonds Mediate Most Protein: DNA and Protein iProtein Interactions

As we will see throughout the book, interactions between proteins and DNA, and between proteins and other proteins, lie at the heart of bow* cells detect and respond to signals, express genes, replicate, repair, and recombine their DNA, and so on—as well as how those processes are regulated. Again, these interactions are mediated by weak chemical bonds of the sorl we have described in this chapter, Despite the low? energy of each individual bond, affinity in these interactions, and specificity as well, results from the combined cffects of many such bonds between any two interacting molecules.

In Chapter 5 we return to these matters with a detailed look at how proteins axe built, how they adopt particular structures, and how they bind DNA and each other.

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