Conformations proline

Glycine residues have more conformational freedom than any other amino acid, as discussed in Chapter 1. A glycine residue at a specific position in a protein has usually only one conformation in a folded structure but can have many different conformations in different unfolded structures of the same protein and thereby contribute to the diversity of unfolded conformations. Proline residues, on the other hand, have less conformational freedom in unfolded structures than any other residue since the proline side chain is fixed by an extra covalent bond to the main chain. Another way to decrease the number of possible unfolded structures of a protein, and hence stabilize the native structure, is, therefore, to mutate glycine residues to any other residue and to increase the number of proline residues. Such mutations can only be made at positions that neither change the conformation of the main chain in the folded structure nor introduce unfavorable, or cause the loss of favorable, contacts with neighboring side chains. 

Proline is relatively compact because of the cyclic nature of its side chain It has less conformational flexibility than the other ammo acids and the presence of proline affects the shape of a peptide more than other ammo acids... 

Figure 6.9 (a) Peptide units can adopt two different conformations, trans and cis. In the trans-form the C=0 and the N-H groups point in opposite directions whereas in the c/s-form they point in the same direction. For most peptides the trans-form is about 1000 times more stable than the c/s-form. (b) When the second residue in a peptide is proline the trans-form is only about four times more stable than the c/s-form. C/s-proline peptides are found in many proteins. 

Sutoh and Noda154 succeeded in proving, by synthesizing block copolymers of the structure (Gly-Pro-Pro)n(Gly-Ala-Pro)m-(Gly-Pro-Pro)n, that with increasing imino add content, AS° changes to higher positive values. They do, however, not relate this to lower entropy losses of conformation but to hydrophobic interactions of the proline residues in the helical state. 

Haasnoot, C. A. G., De Leeuw, F. A. A. M., De Leeuw, H. P. M., Altona, C. Relationship between proton-proton NMR coupling constants and substituent electronegativities. III. Conformational analysis of proline rings in solution using a generalized Karplus equation. Biopolymers 1981, 20,1211-1245. 

The strategy of introducing non-natural aminoacids into the oxytocin peptide skeleton in order to make antagonists has also been exploited by Havaas et al. [51], who replaced the proline at the 7-position with sarcosine and modified the tyrosine residue at the 2-position to introduce further conformational constraint. A representative example is shown, (13), with a... 

Textbook discussions of the steric effects of side chains on backbone conformation convey the impression that, except for glycine and proline, all side chains restrict the allowed range of phi and psi to approximately the same extent. If this were true, encoding of long-range structure by local steric repulsion would seem unlikely. 

The Pn conformation of poly-L-proline (PP) or collagen in the solid state could be identified from X-ray fiber diffraction results (Cowan and McGavin, 1955). Persistence of this basic structure in solution was inferred from the resemblance between the CD spectra of solutions and films of the polypeptide. The CD spectra of the charged forms of PGA and PL closely resemble that of Pn (compare Fig. IB, 1C, and ID) however, these spectra differ significantly from those of PP peptides at high temperature or in the presence of high concentration of salts... 

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