Globular Protein Enzymes

Quite a lot of proteins have a globular structure. Above all, these include enzymes which catalyze all kinds of chemical reactions in a living cell, in particular biosynthesis of new proteins and DNA. Remember that a catalyst is a substance that speeds up a chemical (or some other) reaction, but is not itself a↵ected by the reaction. A light-hearted example is a subway escalator. Its function is to take passengers up and down. Let’s think of these two operations as of two “reactions” going in opposite directions:

[person in subway] + [electrical energy] [person above ground]

From the point of view of energy conservation, it is all very simple and straightforward. If a person is in the subway and there is enough electrical energy available, then he or she can be moved to the surface (the direct

“reaction”). Alternatively, if the person was on the surface and is going down, then his or her potential energy can be transformed into electrical energy (the reverse “reaction”). The escalator itself would not be a↵ected by taking passengers up and down. This is exactly what a typical catalyst does. You can come up with many more such examples for yourself. In fact, any kind of machine tool acts as a catalyst. By the way, biological enzymes behave more like man-made machines, rather than like ordinary chemical catalysts (such as, say, a platinum powder which speeds up the

76 Giant Molecules: Here, There, and Everywhere

oxidation of sulphur dioxide to sulphur trioxide by nearly 1,000 times, and is used in the industrial production of sulphuric acid).

There are two fundamental similarities between enzymes and machines.

First of all, the acceleration of the reaction is extremely high. Usually the reaction does not even occur without the enzyme, in the same way as a rod does not spontaneously shape itself into a bolt without a lathe! The second point in common is the extreme selectivity. An enzyme may work with one substance, but would not work with another, even a very similar one. It is like a cutting tool which cuts right-handed bolts of a certain diameter, but would not make left-handed ones or the ones of even slightly di↵erent diameter.

So how do these molecular machines, the enzyme globules, actually work? Figure 5.15 shows the mechanism schematically. A “starter”

molecule is to undergo the treatment. It dives into a special cavity, or a pocket, on the surface of the globule which is called an active center.

Inside the pocket, the molecule might press a kind of “button”, and some-times the name of active center is reserved for that. Whatever terminology we use, the essence of the matter is that the electron shells of the active center are set into fast motion; then other parts of the globule start moving (although not as fast). They squeeze the “starter” molecule as if with a pair of pincers and pull it, snap it, wring it, and so forth, to make it into the desired shape. In a similar fashion, other proteins fight the “invaders” of our body, such as bacteria and viruses; these proteins are capable of highly specific recognition of other molecules. In fact, the particular protein illus-trated in Figure C5.14 is a “recognition molecular machine”, and the figure depicts how the recognition is achieved in this case.

Certainly, our description of enzymes and immunoglobulines is rather approximate. On the other hand, a detailed theory of how these proteins really work has not yet been completed. This study forms a subject called enzymology. In any case, what seems apparent at this stage is that since each tool or machine is not just a random pile of bits and pieces, similarly an

Fig. 5.15 A sketch of dif-ferent stages of catalysis by an enzyme.

Fig. 5.16 A sketch of a pro-tein crystal.

enzyme’s globule should be an organized structure, with all the monomers in well defined places.

This conclusion can be easily tested by experiment. If it is true, then all the molecules of a particular protein should be globules of a strictly identical shape. Therefore, if they are fairly concentrated they would line up in a regular periodic lattice (as in Figure 5.16), a protein crystal. This is exactly what happens. If you extract a protein from a cell and make a concentrated solution, then after some skilful work (aimed at precise determination of properly conducive conditions, such as temperature, salin-ity, pH — which frequently have to fit into very narrow “windows”), you end up with protein crystals. They are so perfect that they can provide sharp di↵raction patterns when illuminated with X-rays. It is worth to emphasize that not only globules form a regular lattice, but every internal element of every particular globule is positioned inside the globule in ex-actly the same way as its counterparts in all other globules. Studying such di↵raction patterns is a good way to find out the spatial structure of the globules. This is just what the scientists do; as a matter of fact, several thousands of tertiary protein structures have already been “decoded” by now.

So what are the forces that hold a protein in the shape of a globule?

The globule must be very dense since all the monomers have to occupy fixed positions. It turns out that the shrinking of the protein molecule to a globule is mainly caused by the hydrophobic e↵ect which we have already discussed. About a half of all the twenty amino acid residues are hydrophobic, so they are crammed into the inside of the globule, letting the hydrophilic ones take up positions on the surface. This arrangement reminds us of spherical micelles (Figures 5.1 d and C5.2 a). The only di↵erence is that now we have only one long chain strung back and forth through the globule. Thus the structure is not quite spherical, but much more complex.

78 Giant Molecules: Here, There, and Everywhere

We can now understand better some of the difficulties of protein engi-neering. The aim is to design the primary structure so that the chain will coil up into a globule with the required tertiary structure, and will act in the desired way. It is no easier than to write a decent book on polymer physics in a language that seems like gibberish, just by manipulating letters and words randomly!