Proline residues ribonuclease

Proline is an exceptional amino acid residue in that the cis-trans equilibrium only slightly favors the trans form in peptidyl-proline bonds. Small proline-containing peptides in solution contain some 5 to 30% of the cis (syn) isomer, as opposed to less than 0.1% of the cis isomers of the other amino acids.14 The cis form is even found in native proteins two of the four prolines in ribonuclease A... 

Figure 5 Consensus structured regions (CSRs) predicted by the analysis of families of homologous proteins (a) cytochrome c family (b) mammalian ribonuclease family. The CSRs are shown (in bold) as independent segments and are also highlighted on the ribbon drawing of the entire chain. The numbers indicate the residues delimiting the CSRs in the reference structures (cytochrome c2 and bovine ribonuclease. respectively). Proline residues are displayed in full atomic detail and highlighted in view of the effect that proline cis/trans isomerization could have on the formation of early-folding intermediates ...

The cis-conformation of the peptide bond has been observed in globular proteins for a small number of proline residues. It was reported to occur in ribonuclease (Wyckoff et al, 1970), erythrocruorin (Huber et al., 1971), subtilisin (Alden et al., 1973), thermolysin (Matthews et al, 1974), the Bence-Jones dimer REI (Huber and Steigemann, 1974), and carbonic anhydrase (Kannan et al, 1975). One nonproline cis conformation was reported for carboxypeptidase involving the bond between Ser 197 and Tyr 198 (Hartsuck and Lipscomb, 1971). The rare occurrence of cis peptide units is only partially explained by the intrinsic energy of the cis over the trans conformation which is small in proteins (Zimmerman and Scheraga, 1976 see also Section 2.3.2). As reported by Ramanchandran and Mitra (1976), an additional factor is the conformational restriction imposed by the occurrence of a cis peptide unit in a chain of trans units. 

Each protein has, within this general pattern, its own characteristic radical distribution. In ribonuclease, lysine exhibits a much higher activity than do the remaining amino acids. Lysine and methionine are the most heavily labeled residues in lysozyme. In myoglobin, histidine has the highest activity. Methionine is the most heavily labeled amino acid in chymotrypsinogen, as is proline in insulin. Despite the similarities, therefore, each native protein exhibits a characteristic tritium distribution. 

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