Tertiary protein structure hydrophobic interactions

Chemical immobilization methods may alter the local and net charges of enzymes, through covalent modification of charged residues such as lysine (NH4), aspartate, and glutamate (COO-). Conformational changes in secondary and tertiary protein structure may occur as a result of this covalent modification, or as a result of electrostatic, hydrogen-bonding or hydrophobic interactions with the support material. Finally, activity losses may occur as a result of the chemical transformation of catalytically essential amino acid residues. 

The enrichments and depletions displayed in Figure 1 are concordant with what would be expected if disorder were encoded by the sequence (Williams et al., 2001). Disordered regions are depleted in the hydrophobic amino acids, which tend to be buried, and enriched in the hydrophilic amino acids, which tend to be exposed. Such sequences would be expected to lack the ability to form the hydrophobic cores that stabilize ordered protein structure. Thus, these data strongly support the conjecture that intrinsic disorder is encoded by local amino acid sequence information, and not by a more complex code involving, for example, lack of suitable tertiary interactions. 

The van der Waals model of monomeric insulin (1) once again shows the wedge-shaped tertiary structure formed by the two chains together. In the second model (3, bottom), the side chains of polar amino acids are shown in blue, while apolar residues are yellow or pink. This model emphasizes the importance of the hydrophobic effect for protein folding (see p. 74). In insulin as well, most hydrophobic side chains are located on the inside of the molecule, while the hydrophilic residues are located on the surface. Apparently in contradiction to this rule, several apolar side chains (pink) are found on the surface. However, all of these residues are involved in hydrophobic interactions that stabilize the dimeric and hexameric forms of insulin. 

The tertiary structure of native proteins is stabilized through hydrophobic interactions in the interior of the three-dimensional structure. The strongly hydrophobic conditions of RPC are known to unfold this conformation. With some species, e.g., with lysozyme, the unfolding is reversible. Here, even RPC does not produce permanently deactivated species but, in general, unfolding causes denaturation. 

Specificity of conventional protein enzymes is provided by precise molecular fit. The mutual recognition of an enzyme and is substrate is the result of various intermolecular forces which are almost always strongly dominated by hydrophobic interaction. In contrast, specificity of catalytic RNAs is provided by base pairing (see for example the hammerhead ribozyme in Figure 1) and to a lesser extent by tertiary interactions. Both are the results of hydrogen bond specificity. Metal ions too, in particular Mg2+, are often involved in RNA structure formation and catalysis. Catalytic action of RNA on RNA is exercised in the cofolded complexes of ribozyme and substrate. Since the formation of a ribozyme s catalytic center which operates on another RNA molecule requires sequence complementarity in parts of the substrate, ribozyme specificity is thus predominantly reflected by the sequence and not by the three-dimensional structure of the isolated substrate. 

Hydrophobic interactions are formed when two or more hydrophobic groups (for example, side chains of valine, leucine, phenylalanine, and so on) in an aqueous environment find themselves sufficiently close to exclude water molecules from their vicinity. These interactions are primarily a result of entropy effects and are believed to be of major importance in the maintenance of the tertiary structures of proteins. Scheraga and coworkers have also proposed that hydrophobic interactions may be involved in the stabilization of the a helix and the pleated sheet structures. 

Secondary, tertiary, and quaternary structures of a protein are mainly stabilized by hydrophobic interactions, van der Waals forces, and by hydrogen bonds. 

The conformation of a protein in a particular environment affects its functional properties. Conformation is governed by the amino acid composition and their sequence as influenced by the immediate environment. The secondary, tertiary and quaternary structures of proteins are mostly due to non-covalent interactions between the side chains of contiguous amino acid residues. Covalent disulfide bonds may be important in the maintenance of tertiary and quaternary structure. The non-covalent forces are hydrogen bonding, electrostatic interactions, Van der Waals interactions and hydrophobic associations. The possible importance of these in relation to protein structure and function was discussed by Ryan (13). 

The maintenance of tertiary and quartemary structure of polypeptides and proteins, as well as their mechanisms of association with other cellular components, is known to be, in part, mediated by hydrophobic interactions. In fact, the most important single factor in the organization of the constituent molecules of living matter into complex structural entities and the subsequent transmission of the encoded information from one structure to another is probably the hydrophobic effect. Consequently, it is not surprising that separative methods should have been developed which exploit this phenomenon. 

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