Protein hydrophobic bond

Effect of Temperature and pH. The temperature dependence of enzymes often follows the rule that a 10°C increase in temperature doubles the activity. However, this is only tme as long as the enzyme is not deactivated by the thermal denaturation characteristic for enzymes and other proteins. The three-dimensional stmcture of an enzyme molecule, which is vital for the activity of the molecule, is governed by many forces and interactions such as hydrogen bonding, hydrophobic interactions, and van der Waals forces. At low temperatures the molecule is constrained by these forces as the temperature increases, the thermal motion of the various regions of the enzyme increases until finally the molecule is no longer able to maintain its stmcture or its activity. Most enzymes have temperature optima between 40 and 60°C. However, thermostable enzymes exist with optima near 100°C. 

Several different kinds of noncovalent interactions are of vital importance in protein structure. Hydrogen bonds, hydrophobic interactions, electrostatic bonds, and van der Waals forces are all noncovalent in nature, yet are extremely important influences on protein conformations. The stabilization free energies afforded by each of these interactions may be highly dependent on the local environment within the protein, but certain generalizations can still be made. 

It is well known the tendency of polysaccharides to associate in aqueous solution. These molecular associations can deeply affect their function in a particular application due to their influence on molecular weight, shape and size, which determines how molecules interact with other molecules and water. There are several factors such as hydrogen bonding, hydrophobic association, an association mediated by ions, electrostatic interactions, which depend on the concentration and the presence of protein components that affect the ability to form supramolecular complexes. 

As we have just seen, the initial encounter complex between an enzyme and its substrate is characterized by a reversible equilibrium between the binary complex and the free forms of enzyme and substrate. Hence the binary complex is stabilized through a variety of noncovalent interactions between the substrate and enzyme molecules. Likewise the majority of pharmacologically relevant enzyme inhibitors, which we will encounter in subsequent chapters, bind to their enzyme targets through a combination of noncovalent interactions. Some of the more important of these noncovalent forces for interactions between proteins (e.g., enzymes) and ligands (e.g., substrates, cofactors, and reversible inhibitors) include electrostatic interactions, hydrogen bonds, hydrophobic forces, and van der Waals forces (Copeland, 2000). 

The active site of an enzyme is generally a pocket or cleft that is specialized to recognize specific substrates and catalyze chemical transformations. It is formed in the three-dimensional structure by a collection of different amino acids (active-site residues) that may or may not be adjacent in the primary sequence. The interactions between the active site and the substrate occur via the same forces that stabilize protein structure hydrophobic interactions, electrostatic interactions (charge-charge), hydrogen bonding, and van der Waals interactions. Enzyme active sites do not simply bind substrates they also provide catalytic groups to facilitate the chemistry and provide specific interactions that stabilize the formation of the transition state for the chemical reaction. 

The native conformation of proteins is stabilized by a number of different interactions. Among these, only the disulfide bonds (B) represent covalent bonds. Hydrogen bonds, which can form inside secondary structures, as well as between more distant residues, are involved in all proteins (see p. 6). Many proteins are also stabilized by complex formation with metal ions (see pp. 76, 342, and 378, for example). The hydrophobic effect is particularly important for protein stability. In globular proteins, most hydrophobic amino acid residues are arranged in the interior of the structure in the native conformation, while the polar amino acids are mainly found on the surface (see pp. 28, 76). 

Hydrophobic dehydration results from bonding of the protein s hydrophobic patches to the hydrophobic regions on the adsorbent. The enthalpic part of this interaction is small the entropy change is positive. Hydrophobic dehydration is relatively unimportant for hydrophilic surfaces and/or rigid hydrophilic proteins. 

In addition to the peptide bonds between individual amino acid residues, the three-dimensional structure of a protein is maintained by a combination of noncovalent interactions (electrostatic forces, van der Waals forces, hydrogen bonds, hydrophobic forces) and covalent interactions (disulfide bonds). 

Proteins containing more than one polypeptide chain, such as hemoglobin (see Topic B4), exhibit a fourth level of protein structure called quaternary structure (Fig. 8). This level of structure refers to the spatial arrangement of the polypeptide subunits and the nature of the interactions between them. These interactions may be covalent links (e.g. disulfide bonds) or noncovalent interactions (electrostatic forces, hydrogen bonding, hydrophobic interactions). 

As with the majority of transmembrane proteins, the hydrophobic membrane-spanning region consists mainly of amino acid residues with hydrophobic side-chains that are folded in an a-helical conformation (see Topic B3). As each amino acid residue adds 0.15 nm to the length of an a-helix, a helix of 25 residues would have a length of 3.75 nm, just enough to span the hydrophobic core of the bilayer. The hydrophobic side-chains of the residues in the helix protrude outwards from the helix axis to interact via hydrophobic bonds with... 

Fig. 5.3 Comparison of the theoretical and experimental 3D structure (ribbon representation) of the putative nitroreductase, one of the targets of CASP6 competition. The energy expression which was used in theoretical calculations takes into account the physical interactions (such as hydrogen bonds, hydrophobic interactions, etc.) as well as an empirical potential deduced from representative proteins experimental structures deposited in the Brookhaven Protein Data Bank (no bias towards the target protein), (a) Predicted by Kolinski and Bujnicki [11] by the Monte Carlo method, and (b) determined experimentally by X-ray diffraction [12]. Both structures in atomic resolution differ (r.m.s.) by 2.9A. Reproduced by courtesy of Professor Andrzej Kolinski...

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