Native conformation of protein

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). 

Information about the biologically active (native) conformation of proteins is already encoded in their amino acid sequences. The native forms of many proteins arise spontaneously in the test tube and within a few minutes. Nevertheless, there are special auxiliary proteins (chaperonines) that support the folding of other proteins in the conditions present within the cell (see p. 232). An important goal of biochemistry is to understand the laws governing protein folding. This would make it possible to predict the conformation of a protein from the easily accessible DNA sequence (see p. 260). 

Change in the native conformation of proteins or nucleic acids resulting in loss of their biological activity. 

About 200 to 460 kJ/mol are required to break a single covalent bond, whereas weak interactions can be disrupted by a mere 4 to 30 kJ/mol. Individual covalent bonds that contribute to the native conformations of proteins, such as disulfide bonds linking separate parts of a single polypeptide chain, are clearly much stronger than individual weak interactions. Yet, because they are so numerous, it is weak interactions that predominate as a stabilizing force in protein structure. In general, the protein conformation with the lowest free energy (that is, the most stable conformation) is the one with the maximum number of weak interactions. 

In anticipation of the discussion to be presented in Section IV, it is important to realize that the native conformations of proteins are almost always altered in nonaqueous solvents, and the conformation of any one protein may be different in different solvents. The solubility of a protein might well depend on conformation, since the latter should determine the nature of solute-solvent interactions. Particularly as a result of this additional complication, the solubility of proteins in weakly protic solvents can only be approached in a wholly empirical manner. 

Only pK values observed for the native conformation of proteins are listed. A value of is used to indicate that a group appears incapable of dissociation in the native molecule, a value of — w that it appears incapable of binding a proton. References to all data are given in Section X. 

Some food proteins are rich in phosphoric acid residues. The acid may either form ester bonds with Ser residues, as in caseins and egg proteins, or stabilize the native conformation of protein micelles by electrostatic interactions with negatively charged groups and calcium ions, as in caseins. In soy proteins Ser and Thr residues can be esterihed and Lys amidated with cyclic sodium trimetaphosphate at pH 11.5 and 35°C (Sung et al., 1983) ... 

The binding protein often loses its affinity because of effects of proteases or during extraction (e.g., during extraction of membranes with detergents). Protease inhibitors help, or 10% glycerine (stabilizes the native conformation of proteins). 

In all the methods discussed above, the docking procedirre involved docking of ligands to the native conformation of protein termed as self-docking. There is another... 

Take as a whole, these results on the 5 -GMP self-assembly point to the considerable importance of ion binding to the stability of a supra-molecular structure devoid of covalent bonding. Likewise, the native conformation of proteins benefits to a very significant extent from the presence of salt bridges, bringing together selected groups(47). 

Solvation contributions are generally believed to be a significant force in stabilizing the native conformations of proteins. Explicit methods can be used to include solvation effects by actually surrounding the polypeptide with solvent... 

Simplistically stated, the hydrophobic effect may be defined as the tendency of water to reject any contact with substances of a nonpolar or hydrocarbon nature. The existence of this effect was first recognized in the study of the extremely low solubility of hydrocarbons in water. The principles involved were later successfully applied to the elucidation of the native conformation of protein molecules by Kauz-mann The application of these ideas to the study of membrane structures has been advanced by Singer. Recently, Tanford published an entire book on the hydrophobic effect, including the influence of this interaction on the formation of micelles, lipid bilayers, membranes and other ordered structures. Aside from Singer s and Tanford s" statements on the decisive role of the hydrophobic effect on lyotropics, the lyotropic liquid-crystal literature seems peculiarly unaware of this phenomenon. Winsor s extensive review with its systematic analysis (R-theory) of the many lyotropic phases does not take the hydrophobic effect into account. More recent reviews of lyotropic liquid crystals do not mention the phenomenon. We hope that the present discussion will help to advance the realization of the importance of the hydrophobic effect to lyotropics. The material of the following sections is taken chiefly from Ref. [3] with some assistance from Refs. [2] and [4]. 

The relationship between the amino acid sequence and the structure of the native conformation of proteins represents the key unsolved problem of biochemistry and biology. Temperature and chemical perturbation represent the usual approach used in studies of protein stability and the folding problem. However, it is advantageous to use pressure to study protein solutions as pressure perturbs the protein environment in a controlled way by changing... 

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