Protein stability globular proteins

Salting-out salts (Na2S04, NaCl, MgS04) Surface tension increase Weak binding Stabilize globular proteins and precipitants of native and denatured proteins... 

The interactions between the amino acids and the solvent (electrostatic, hydrophilic, hydrophobic, S-S) determine the globular conformation. We can give some naive picture of the folded state in terms of a liquid-hydrocarbon model where the hydrophobic core stabilizes globular proteins. The hydrophilic (polar and charged) amino acids are exposed to the solvent and the hydrophobic (polar) amino acids are less exposed to the solvent and buried in the interior of the protein. 

Myers, J.K. Pace, C.N. Hydrogen bonding stabilizes globular proteins. Biophysical Journal, 1996, 71, 2033—2039. 

The behaviour of tliese systems is similar to tliat of suspensions in which short-range attractions are induced by changing solvent quality for sterically stabilized particles (e.g. [103]). Anotlier case in which narrow attractions arise is tliat of solutions of globular proteins. These crystallize only in a narrow range of concentrations [104]. 

Water-soluble globular proteins usually have an interior composed almost entirely of non polar, hydrophobic amino acids such as phenylalanine, tryptophan, valine and leucine witl polar and charged amino acids such as lysine and arginine located on the surface of thi molecule. This packing of hydrophobic residues is a consequence of the hydrophobic effeci which is the most important factor that contributes to protein stability. The molecula basis for the hydrophobic effect continues to be the subject of some debate but is general considered to be entropic in origin. Moreover, it is the entropy change of the solvent that i... 

Dill, KA. Theory for the folding and stability of globular proteins. Biochemistry 24 1501-1509, 1985. 

Hydrogen bonding stabilizes some protein molecules in helical forms, and disulfide cross-links stabilize some protein molecules in globular forms. We shall consider helical structures in Sec. 1.11 and shall learn more about ellipsoidal globular proteins in the chapters concerned with the solution properties of polymers, especially Chap. 9. Both secondary and tertiary levels of structure are also influenced by the distribution of polar and nonpolar amino acid molecules relative to the aqueous environment of the protein molecules. Nonpolar amino acids are designated in Table 1.3. 

With a knowledge of the methodology in hand, let s review the results of amino acid composition and sequence studies on proteins. Table 5.8 lists the relative frequencies of the amino acids in various proteins. It is very unusual for a globular protein to have an amino acid composition that deviates substantially from these values. Apparently, these abundances reflect a distribution of amino acid polarities that is optimal for protein stability in an aqueous milieu. Membrane proteins have relatively more hydrophobic and fewer ionic amino acids, a condition consistent with their location. Fibrous proteins may show compositions that are atypical with respect to these norms, indicating an underlying relationship between the composition and the structure of these proteins. 

Figure 26.5 (a) The o-helical secondary structure of proteins is stabilized by hydrogen bonds between the N—H group of one residue and the C=0 group four residues away, (b) The structure of myoglobin, a globular protein with extensive helical regions that are shown as coiled ribbons in this representation. 

Dantas G, Kuhlman B, Callender D, Wong M, Baker D. A large scale test of computational protein design folding and stability of nine completely redesigned globular proteins. J Mol Biol 2003 332 449-60. 

Globular proteins are known to act as polymeric stabilizers of protein structure in solution. Wang and Hanson [106] review the mechanisms of protein stabilization by serum albumin, and it has been included in... 

I Sugars (sucrose, glucose, mannose) Surface tension increase Inert Good stabilizers of globular proteins and assembled organelles... 

Some amino acids (glycine, alanine, glutamic, and aspartic acids) Surface tension increase Weak binding Stabilizers of globular proteins... 

Glycerol, polyols (sorbitol, mannitol) Solvophobicity Affinity for polar regions Stabilizers of globular proteins and assembled organelles, decreasing for proteins of high polarity... 

The structure and structural stability of globular proteins in aqueous solution are the result of various interactions inside the protein molecule, between the protein and the water, and among the water molecules (Norde 2003a). The... 

Enzymes are biological catalysts in the form of globular proteins, and in liquid detergent compositions enzymes have inherent stability problems since the proteases not only digest the protein stains, but also the other enzymes. If this destructive mechanism is not controlled, the enzymes in the liquid detergent composition will have unacceptably short storage stability. 

Figure 11.5 Globular proteins. The folding of a polypeptide chain in a globular form is stabilized by hydrophobic interactions and some covalent bonding, particularly the disulphide bond between cysteine residues. The polypeptide chain shows some sections which are regular and helical in nature and other sections, particularly at bends and folds, where the conformation of the chain is distorted.

The nature of the amino acid residues is of prime importance in the development and maintenance of protein structure. Polypeptide chains composed of simple aliphatic amino acids tend to form helices more readily than do those involving many different amino acids. Sections of a polypeptide chain which are mainly non-polar and hydrophobic tend to be buried in the interior of the molecule away from the interface with water, whereas the polar amino acid residues usually lie on the exterior of a globular protein. The folded polypeptide chain is further stabilized by the presence of disulphide bonds, which are produced by the oxidation of two cysteine residues. Such covalent bonds are extremely important in maintaining protein structure, both internally in the globular proteins and externally in the bonding between adjacent chains in the fibrous proteins. 

Privalov, P.L. 1979. Stability of proteins small globular proteins. Adv Protein Chem 33 167-241. 

Ganesh, C., N. Eswar, S. Srivastava, C. Ramakrishnan, and R. Varadarajan. 1999. Prediction of the maximal stability temperature of monomeric globular proteins solely from amino acid sequence. FEBS Lett 454 31-36. 

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