Secondary protein structure coil conformation

Fig. 44. Distribution of Ala in the Ramachandran plot when using (A) all secondary structure conformations in the protein database or (B) only those Ala residues in a coil conformation. (From Serrano, 1995. 1995, with permission from Academic Press.)...

Before doing so, we briefly examine the influence of conformation and flexibility. Indeed, formation of succinimide is limited in proteins due to conformational constraints, such that the optimal value of the and ip angles (Sect. 6.1.2) around the aspartic acid and asparagine residues should be +120° and -120°, respectively [99], These constraints often interfere with the reactivity of aspartic acid residues in proteins, but they can be alleviated to some extent by local backbone flexibility when it allows the reacting groups to approach each other and, so, favors the intramolecular reactions depicted in Fig. 6.27. When compared to the same sequence in more-flexible random coils, elements of well-formed secondary structure, especially a-helices and 13-turns, markedly reduce the rate of succinimide formation and other intramolecular reactions [90][100],... 

Independently, Ruan etal. (1990) demonstrated that unnatural metal-ligating residues may likewise be utilized toward the stabilization of short a helices by transition metal ions (including Zn " ")—these investigators reported that an 11-mer is converted from the random coil conformation to about 80% a helix by the addition of Cd at 4°C. These results suggest that the engineering of zinc-binding sites in small peptides or large proteins may be a powerful approach toward the stabilization of protein secondary structure. 

NMR and kinetic studies have been conducted with the hope of providing more details about the position and conformation of the polypeptide substrate in cAMP-dependent protein kinase. These have served to narrow down the possible spatial relationships between enzyme bound ATP and the phosphorylated serine. Thus, a picture of the active site that is consistent with the available data can be drawn (12,13,66,67). Although these studies have been largely successful at eliminating some classes of secondary polypeptide structure such as oi-hellces, 6-sheets or an obligatory 6-turn conformation 66), the precise conformation of the substrate is still not known. The data are consistent with a preference for certain 6-turn structures directly Involving the phosphorylated serine residue. However, they are also consistent with a preference or requirement for either a coil structure or some nonspecific type of secondary structure. Models of the ternary active-site complexes based on both the coil and the, turn conformations of one alternate peptide substrate have" been constructed (12). These two models are consistent with the available kinetic and NMR data. 

Approximately one half of an average globular protein is organized into repetitive structures, such as the a-helix and/or 3-sheet. The remainder of the polypeptide chain is described as having a loop or coil conformation. These nonrepetitive secondary structures are not... 

As a prelude to discussing the mechanism of folding of intact proteins in the next chapter, we end this one with a discussion of the kinetics and mechanism of folding of isolated secondary structural elements of proteins from the random coil conformation. 

Two of the hydrophihcity scales in Table 2 were derived from experimental measures of the behavior of amino acids in various solvents, namely partitioning coefficients [K-D index of Kyte and Doolittle (30)] or mobility in paper chromatography [Rf index of Zimmerman et al. (31)]. By contrast, the Hp index was obtained from quantum mechanics (QM) calculations of electron densities of side chain atoms in comparison with water (32). The Hp index is correlated highly with these two established hydrophobicity scales (Table 4). Therefore, like the polarizability index, it is possible to represent fundamental chemical properties of amino acids (hydrophUicity, Hp) with parameters derived from ab initio calculations of electronic properties. However, in contrast to polarizabihty (steric effects), hydrophihcity shows significant correlation with preference for secondary structure. Thus, hydrophobic amino acids prefer fi-strands (and fi-sheet conformations) and typically are buried in protein structures, whereas hydrophilic residues are found commonly in turns (coil structure) at the protein surface. 

Studies by Anfinsen of the reversible denaturation of the pancreatic enzyme ribonuclease prompted the hypothesis that secondary and tertiary structures are derived inclusively from the primary structure of a protein (Figures 4-11 and 4-12). RNase A, which consists of a single polypeptide chain of 124 amino acid residues, has four disulfide bonds. Treatment of the enzyme with 8 M urea, which disrupts noncovalent bonds, and j8-mercaptoethanol, which reduces disulfide linkages to cysteinyl residues, yields a random coil conformation. 

Swindells et al. [120] have calculated the intrinsic , i// propensities of the 20 amino acids from the coil regions of 85 protein structures. The distribution for coil regions is quite different than for the regular secondary structure regions, with a large increase in flP and oq conformations and much more diverse conformations in the pE and aR regions. Their results also indicate that the 18 non-Gly, Pro amino acid type are in fact quite different from each other in terms of their Ramachandran distributions, despite the fact that they are usually treated as identically distributed in prediction methods [95, 121]. Their analysis was divided into the main broad... 

The structure of the native protein can be important in influencing the rate, extent, and effects of denaturation. Proline-rich peptides and proteins capable of a secondary helical structure appear to favor partially folded structures under denaturing conditions these are simultaneously present with random-coil denatured molecules (32). The presence of these two slowly interconverting conformers then leads to increased reversed-phase band broadening as above. Structural factors which disfavor protein denaturation can also operate to reduce band width. For the HIC separation of various apolipoproteins (96), it was found that more hydrophobic proteins gave narrower bands. This was attributed to a more structure conformer in the retained state for the more hydrophobic protein. That is, a single (native ) conformer exists during the separation of more hydrophobic proteins in this system, but some denaturation of less hydrophobic proteins occurs. 

A schematic comparison of the levels of protein structure. Primary structure is the covalently bonded structure, including the amino acid sequence and any disulfide bridges. Secondary structure refers to the areas of a helix, pleated sheet, or random coil. Tertiary structure refers to the overall conformation of the molecule. Quaternary structure refers to the association of two or more peptide chains in the active protein. 

The secondary structure covers the spatially arranged conformations produced by hydrogen bonding between peptide bonds such as helix sequences and pleated sheet structures. Here, the tendency toward helix formation for the same amino acid residues in poly(a-amino acids) and proteins is mostly, but not always, of the same magnitude (Table 30-1). The peptide chains in the pleated sheet structure are mainly arranged antiparallel. Segments in the coil conformation are generally not included in the secondary structure. 

Figure 7. A list of frequent residue exchanges in making secondary structural transitions in pentapeptide pairs of unrelated protein structures. The pentapeptides differed by only one amino acid. The terms H, E, T, 0, refer respectively to helix, strand, turn conformations and other unclassifiable structures (coil).

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