Native state of protein

Although all proteinogenic amino acids form predominantly anti peptide bonds, a search in the Brookhaven Protein Database revealed that approximately 6-7% of all X-prolyl peptide bonds are found in the syn conformation in the native state of proteins [8]. The reason for this relatively frequent occurrence of syn-prolyl peptide bonds lies in steric repulsion of the proline 3 protons and the adjacent N-terminal amino acid in the anti conformation, resulting in a low barrier of rotation and energetically similar syn and anti isomers (Figure 1.2.3). 

Extrinsic factors stabilizing the native state of proteins at high temperatures... 

Dadarlat and Post [57] have found an interesting correlation between the heat capacity changes of unfolding and the compressibility of the native state of proteins. This can be rationalized from a similar dependence of these quantities on the distribution of the atom types, polar/charged versus nonpolar. 

In this equation Ap is the compressibility factor difference (P =PV) and Aa the difference of the thermal expansion factor (a =aV) of the denatured and native states of proteins. An important assumption in the derivation of this equation is the temperature and pressure independence of Aa, AP and ACp. The AG=0 curve is an ellipse on the P-T plane and it describes the equilibrium border between the native and denatured state of the protein. This curve is known as the phase or stability diagram. This is visualized in Fig. 2. The diagram illustrates the interconnection between the cold, heat and pressure unfolding of proteins. 

It has recently been shown that NMR chemical shifts can be used to determine the structures of the native states of proteins in solution. By considering the cases of two proteins, GBl and SH3, Robustelli et al. provide an initial demonstration that this type of approach can be extended to the use of solid-state NMR chemical shifts to obtain protein structures in the solid state without the need for measuring interatomic distances. ... 

Section 27 22 Many proteins consist of two or more chains and the way in which the various units are assembled m the native state of the protein is called its quaternary structure... 

Fig. 7. Simple schematic diagram representing three conformational states of proteins The expanded denatured state whose structure is determined by steric interactions the compact denatured state, with structure determined by hydrophobic buril and the native state, with structure determined by dispersion forces, hydrogen bonds, and electrostatics.

A long chain of amino acids attached end-to-end has many possible ways to fold. The final shape, or conformation, of a folded protein molecule is determined by its unique sequence of amino acids and by the effects of environmental conditions on amino acid side chains. The conformation selected is the one that is most stable because it has the lowest free energy (Bloomfield 1979). This conformation is designated the native state of the protein. 

The native state of a protein has many of its hydrophobic side chains shielded from water because they are packed in hydrophobic cores. Conversely, the denatured state has many of its hydrophobic side chains exposed to solvent. The water molecules stack around these in icebergs as they maximize their hydrogen bonds with one another (Chapter 11). This lowers the entropy of water, because the individual molecules have less freedom of movement, and lowers the enthalpy because more hydrogen bonds are made.2 Similarly, the hydrogen bond donors and acceptors in the polypeptide backbone of the denatured protein are largely exposed to solvent and tie down more water molecules.3 These water molecules are released as the protein folds, and the gain in entropy of water compensates considerably for the loss of conformational entropy. 

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