The quaternary structure of proteins

One important feature of this tertiary structure is that the centre of the proteins is hydrophobic and non-polar. This has important consequences as far as the action of enzymes is concerned and helps to explain why reactions which should be impossible in an aqueous environment can take place in the presence of enzymes. The enzyme can provide a non-aqueous environment for the reaction to take place. 

Quaternary structure is confined to those proteins which are made up of a number of protein subunits (Fig. 3.15). For example, haemoglobin is made up of four protein molecules—two identical alpha subunits and two identical beta subunits (not to be confused with the alpha and beta terminology used in secondary structure). The quaternary structure of haemoglobin is the way in which these four protein units associate with each other. 

Since this must inevitably involve interactions between the exterior surfaces of proteins, ionic bonding can be more important to quaternary structure than it is to tertiary structure. Nevertheless, hydrophobic (van der Waals) interactions have a role to play. It is not possible for a protein to fold up such that all hydrophobic groups are placed to the centre. Some such groups may be stranded on the surface. If they form a small hydrophobic area on the protein surface, there would be a distinct advantage for two protein molecules to form a dimer such that the two hydrophobic areas face each other rather than be exposed to an aqueous environment. 

We have now discussed the four types of structure. The tertiary structure is the most important feature as far as drug action is concerned, although it must be emphasized 

We are now ready to discuss the two types of protein with which drugs interact— enzymes and receptors. 

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Figure 8.10 The quaternary structure of proteins. The enzyme lactate dehydrogenase (EC 1.1.1.27) has a relative molecular mass of approximately 140 000 and occurs as a tetramer produced by the association of two different globular proteins (A and B), a characteristic that results in five different hybrid forms of the active enzyme. The A and B peptides are enzymically inactive and are often indicated by M (muscle) and H (heart). The A4 tetramer predominates in skeletal muscle while the B4 form predominates in heart muscle but all tissues show most types in varying amounts.

Figure II-4 Examples of the quaternary structure of proteins, (a) A drawing of glutamine synthetase of coli showing the orientation of the 12 identical subunits of the enzyme. (b) A drawing of aspartate transcarbamylase of coli showing the proposed orientation of the 6 catalytic subunits (labeled C, each MW = 33,000), and 6 regulatory subunits (labeled R, each MW =...

Important differences between DNA and RNA appear in their secondary and tertiary structures, and so we shall describe these structural features separately for DNA and for RNA. Even though nothing in nucleic acid structure is directly analogous to the quaternary structure of proteins, the interaction of nucleic acids with other classes of macromolecules (for example, proteins) to form complexes is similar to the interactions of the subunits in an oligomeric protein. One well-known example is the association of RNA and proteins in ribosomes (the polypeptide-generating machinery of the cell) another is the self-assembly of tobacco mosaic virus, in which the nucleic acid strand winds through a cylinder of coat-protein subunits. 

The blue gel is both a new purification method and potentially a means of determining the quaternary structure of proteins (see Chapter 8), especially in combination with an SDS gel— which, as a second dimension, cleaves the natively separated oligomers into their subimits. 

Explain what is meant by the quaternary structure of proteins. (Section 9.9)... 

Explain what is meant by the quaternary structure of proteins. 

H. Sundand K. Weber, The quaternary structure of proteins, Chem. Int. Ed. Engl. 5,121... 

Two polypeptide chains connected by hydrogen bonding form the quaternary structure of protein. 

It has been known for a long time that surfactants could precipitate, form complexes with or denature proteins at low concentrations. Early work with albumin suggested that the presence of a polar group in the surfactant molecule was a prerequisite to interaction with protein. The lack of interaction of nonionic surfactants and proteins, it was implied, had important consequences, since it divorced the non-ionics from biologically deleterious effects such as denatur-ation and inactivation of proteins. This view has since had to be modified as nonionic surfactants are not the mild agents that they appeared to be. Hydrophobic interaction of the hydrocarbon chain of the non-ionic surfactant can result in a modification of the quaternary structure of proteins in solution. Possible modes of interaction of anionic surfactants are shown in Fig. 10.7. 

In addition to the earlier paper by Monod et ai (1965), some reviews of the quaternary structure of proteins have pointed out the importance of the oligomeric structure for the stability and the functional properties of the molecule as well as for its advantage along molecular evolution (see Sund and Weber, 1966 Hanson, 1966, 1968 Klotz et u/., 1970 Matthews and Bernhard, 1973 Friedman and Beychok, 1979). Klug (1967) has discussed the possible geometry for protein oligomers that pertain specifically to virus structure. 

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