Conformational role of His-12 in C-peptide of ribonuclease A.

Possible interactions of the His-12 ring with other side chain and backbone groups of C-peptide lactone (CPL) are discussed. The works published so far are critically reviewed and compared with the latest results obtained by the authors. The main new conclusion is that in the helical conformation of CPL, the Phe-8 and His-12 rings are clustered together. Studies of Phe-8----Ala analogs of CPL and calculations of ring current effects satisfactorily explain the observed environmental shifts of Phe-8 and His-12 protons in NMR spectra of CPL. Interaction between both rings is favorable for alpha-helix formation, but cannot explain an increase in helix stability related with protonation of His-12. This effect arises from favorable interactions of the charged His+-12 ring with the helix backbone.