The tertiary structure of proteins

The tertiary structure is the overall 3D shape of a protein. Structural proteins are quite ordered in shape, whereas other proteins such as enzymes and receptors fold up on themselves to form more complex structures. The tertiary structure of enzymes 

1 Some proteins contain species known as cofactors (e.g. metal ions or small organic molecules) which also have an effect on tertiary structure. 

This poses a problem. Why should a chain of amino acids take up such a precise 3D shape At first sight, it does uot make sense. If we place a length of string on the table, 

The answer lies in the fact that a protein is not just a bland length of string. It has a whole range of chemical functional groups attached dong the length of its chain. 

These are, of course, the residues of each amino acid making up the chain. These residues can interact with each other. Some will attract each other. Others will repel. Thus the protein will twist and turn to minimize the unfavourable interactions and to maximize the favourable ones until the most favourable shape (conformation) is found—the tertiary structure (Fig. 3.7). 

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Cohen, F.E., Sternberg, M.J.E., Taylor, W.R. Analysis of the tertiary structure of protein p-sheet sandwiches. 

The extrusion process frequently results in realignment of disulfide bonds and breakage of intramolecular bonds. Disulfide bonds stabilize the tertiary structure of protein and may limit protein imfolding during extrusion (Taylor et al., 2006). Flow and melt characteristics were improved when other proteins were extruded with disulfide reducing agents (Areas, 1992), which indicates that disulfide bonds adversely affect... 

However, 2D NOE studies are invaluable in structure determination, in particular of peptides and proteins here the NOEs give invaluable information for conformational analysis and the determination of the tertiary structures of proteins. 

Fournier and DePristo96 calculated bond energies in several small compounds containing disulfide bonds which are known to stabilize the tertiary structure of proteins. Bond dissociation energies are generally overestimated when LDA(SVWN) is used whereas the PW86/P86 functional brings them to within 5 kcal/mol of experimental values. 

On a larger scale, the unique folding and structure of one complete polypeptide chain is termed the tertiary structure of protein molecules. The difference between local secondary structure and complete polypeptide tertiary structure is arbitrary and sometimes of little practical difference. 

The influence of secondary structure on reactions of deamidation has been confirmed in a number of studies. Thus, deamidation was inversely proportional to the extent of a-helicity in model peptides [120], Similarly, a-hel-ices and /3-turns were found to stabilize asparagine residues against deamidation, whereas the effect of /3-sheets was unclear [114], The tertiary structure of proteins is also a major determinant of chemical stability, in particular against deamidation [121], on the basis of several factors such as the stabilization of elements of secondary structure and restrictions to local flexibility, as also discussed for the reactivity of aspartic acid residues (Sect. 6.3.3). Furthermore, deamidation is markedly decreased in regions of low polarity in the interior of proteins because the formation of cyclic imides (Fig. 6.29, Pathway e) is favored by deprotonation of the nucleophilic backbone N-atom, which is markedly reduced in solvents of low polarity [100][112],... 

Researchers J, Versieck and L. Vanballenberghe (University Hospital, Ghent. Belgium) have observed, Tin has chemical properties offering potentials for a biological function, The element has a tendency to form truly covalent linkages as well as coordination complexes hence, it was hypothesized that it could well contribute to the tertiary structure of proteins or other biologically important macromolcculcs, such as nucleic acids. 

Changing the environmental conditions can easily provide sufficient energy to alter the tertiary structure of proteins significantly. 

Why is cysteine such an important amino acid for defining the tertiary structure of proteins ... 

Disulfide bond Bonds that form in the tertiary structure of proteins between two sulfur atoms of cysteine amino acids in the polypeptide chains. 

The interactions, such as hydrogen bonding, that dictate the tertiary structure of proteins are not as strong as covalent chemical bonds. Because these interactions are rather weak, they can be disrupted with relatively modest stresses. 

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. 

This expression clearly has parallels with Equation 5 if we interpret adiabatic compressibility, k, as the reciprocal of the elastic modulus, M. This simple equation is the key to an important class of food measurements because k is related to changes in the tertiary structure of proteins, opening up the possibility of rapid characterization and the detection of denaturation (Apenten et al., 2000). For mixtures of materials, Wood (1941) invoked the idea of an effective medium to represent a mixture consisting of particles suspended in a continuum with compressibility and density given as ... 

The presence and biochemical importance of a number of transition metals in proteins has been widely recognized. Various reasons may be assigned for the presence and reactivity of metal ions in proteins 1. Frequently the tertiary structure of proteins is stabilized by metal ions,... 

For most enzymes, catalytic activity is temperature-dependent to a maximum level, above whioh they lose their activity. Also, by analogy with other proteins, enzymes are stable only within a limited range of pH. Outside this range, enzymes are denatured by ohanges in the charges of ionizable amino acid residues that alter the tertiary structure of proteins. Enzyme activity reaches a peak or a plateau at a specific pH, so enzymatic digestion is usually performed in a buffered medium. The process is also affected by the enzyme concentration, which must therefore be optimized as well. 

Give examples of amino acids that could give rise to the interactions pictured in Fig. 22.25 that maintain the tertiary structures of proteins. 

Because of the predominant contribution of conformation to the tertiary structure of protein antigens and because protein antigens may contain several antigenic determinants, the previously described approaches... 

The stereochemical shape concept covers a wide range of possible resolutions, from the details of electron density distributions between pairs of nuclei in relatively small molecules to the structural organization of the tertiary structure of proteins [201-203], the architecture of supramolecular assemblies [204-230], the problems of shape selectivity in reactions of large molecules [231-233], and the intriguing shape features of self-replicating chemical systems [234-239]. In the following chapters we shall discuss various topological shape analysis techniques, suitable for the relevant level of resolution. 

Denaturing agents can destroy the tertiary structure of proteins. Alcohol s antiseptic action results from denaturing of bacterial proteins. Corrosives can cause tissue damage upon accidental exposure. 

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