Tertiary structures, of peptides

It is important to note that the secondary and tertiary structure of peptides to which they are attached may subsequently help in controUing the reactivity of... 

Hydrophobicity is a property shared to varying degrees by most proteins and is imparted primarily through the side chains of neutral aromatic amino acids phenylalanine, tyrosine and tryptophan. By their lower attraction for water molecules, these amino acids tend to link to one another, thus expelling water from the molecule. While hydrophobicity is one of the natural forces that confer stability on the tertiary structure of peptides, it also imparts stability to formed immune complexes and depending on environmental factors, can exist also between different protein molecules. 

H. Kawai, T. Kikuchi, and Y. Okamoto, Protein Engin., 3, 85 (1989). A Prediction of Tertiary Structures of Peptide by the Monte Carlo Simulated Annealing Method. 

When one computes the amino acid substitution observed in protein of spontaneous or experimental TMV mutants, almost all the tryptic polypeptides clearly are subject to substitution except one—peptide IX. Changes in the tertiary structure of peptide IX are fatal to the protein configuration and prevent reaggregation of the RNA and virus protein. Uncoated RNA is rapidly digested by hydrolases. 

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. 

Peptides can undergo a variety of degradation reactions (Fig. 6.4) [6-9], Pathways of physical degradation include aggregation, precipitation, and adsorption. Denaturation, i. e., an often-irreversible alteration of the tertiary structure of a peptide, is also considered a type of physical degradation. These physical reactions fall outside the scope of this work. 

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],... 

In an attempt to separate the domains from the cores, we used limited degradation with several proteases. CBH I (65 kda) and CBH II (58 kda) under native conditions could only be cleaved successfully with papain (15). The cores (56 and 45 kda) and terminal peptides (11 and 13 kda) were isolated by affinity chromatography (15,16) and the scission points were determined unequivocally. The effect on the activity of these enzymes was quite remarkable (Fig. 7). The cores remained perfectly active towards soluble substrates such as those described above. They exhibited, however, a considerably decreased activity towards native (microcrystalline) cellulose. These effects could be attributed to the loss of the terminal peptides, which were recognized as binding domains, whose role is to raise the relative concentration of the intact enzymes on the cellulose surface. This aspect is discussed further below. The tertiary structures of the intact CBH I and its core in solution were examined by small angle X-ray scattering (SAXS) analysis (17,18). The molecular parameters derived for the core (Rj = 2.09 mm, Dmax = 6.5 nm) and for the intact CBH I (R = 4.27 nm, Dmax = 18 nm) indicated very different shapes for both enzymes. Models constructed on the basis of these SAXS measurements showed a tadpole structure for the intact enzyme and an isotropic ellipsoid for the core (Fig. 8). The extended, flexible tail part of the tadpole should thus be identified with the C-terminal peptide of CBH I. 

The primary, secondary, and tertiary structures of the macromolecule surrounding the metal ion, however, make possible an enormous variation in the microenvironment of the metal ion. The microenvironment also consists of amino acids whose side chains (and also perhaps the peptide backbone) can assume a role in a given catalytic reaction in addition to the metal ion. Such variation is not readily achieved in small molecular systems, but many variations in solvent polarity, pH, etc., can be applied to homogeneous catalysts. 

A unique aspect of using protein substrates is that the substrates themselves are so complex. Even a relatively small protein, having say 100 amino acids, has 99 potentially susceptible peptide bonds—and each of these bonds is expected to be unique. This hypothetical protein thus has 99 structurally unique substrates (potential sites for catalysis). The environment surrounding each of the protein s peptide bonds will be dependent on the tertiary structure of the protein, so one must consider, for example, native... 

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