Alanine: from the usual to the unexpected

Abstract

Data from the experiments provides a possibility to talk about anomalously large contribution of alanine to the stability of an alpha-helix and other protein conformations. Independent data (and also experimental ones) suggest that alanine plays an especially big role in stabilization of the alpha-helix. This can be seen through the positive contribution of alanine both to the entropy of the system and to the enthalpy. The high contribution of alanine to the enthalpy of formation of the alpha helix contradicts the generally accepted view that the entropy should decrease during the formation of regular structures in proteins. Among three types of helices in proteins, alanine stabilizes two secondary structures: the alpha helix and the left helix of polyproline II, and in the case of fibrillar proteins, alanine also stabilizes the beta sheet. The stabilizing effect of alanine on the alpha helix structure extends to both natively unfolded proteins and alpha helix-support conjugates. Thus, it is no exaggeration to say that formation of secondary structure relies on alanine. The revealed contradictions are of paradoxical nature and yet there is no interpretation of the above-mentioned findings (first of all, substantiation of the contribution of alanine to the enthalpy of fusion in terms of fundamental physics) so far to resolve them. Meanwhile, the data and comments presented in this work hold out the promise of progress in resolving the revealed contradictions.