Amide Relevant Conformations in Proteins

Additionally, several lines of evidence suggest that the random coil is a left-handed helix with a structure similar to the PP II helix, at least locally. For example, it was shown that for an a-helical polyalanine chain (21 residues), heating transforms this structure into a PP II conformation [122]. This is possibly due to the fact that PP II disrupts water organization less than /i-sheet and a-helical conformation and is therefore favored entropically [123,124]. 

Recently, much effort has been put into predicting the isomeric state of prolyl bonds in proteins [129,130], A program on the basis of a secondary structure information was developed that predicts for a given sequence whether a particular peptide bond is in either cis or trans conformation [131]. 

By use of site-directed mutagenesis in positions covering cis prolyl bonds, the proline has been replaced by nonproline amino acids. It came as a surprise that the secondary amide peptide bond formed in the substitution still adopts the thermodynamically disfavored cis conformation in many cases [25,26,132-135], Thus, to overcome the free energy costs of a cis secondary amide peptide bond of about 15 kj mol-1 the structural consequences favoring the trans conformation must be absent in the folded protein variant. Consequently, the CTI is largely retained in these protein variants [133], 

Folding reactions limited by prolyl isomerizations have the following CTI-specific characteristics [41]  

In most cases, amplitudes of prolyl-limited folding phases do not much vary with initial folding conditions. 

---