Alanine: The Usual and the Unexpected

Abstract

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Based on experimental data, one can note the abnormally large contribution of alanine to the stabilization of the alpha helix and other protein conformations. Independent (including experimental) data indicate a particularly large contribution of alanine to the stabilization of the alpha helix. At the same time, positive contributions were revealed, both to the entropy and to the enthalpy of the system. The high contribution of alanine to the enthalpy of alpha helix formation contradicts the generally accepted view that entropy should decrease during the formation of regular structures in proteins. Alanine stabilizes two types of secondary structure out of three, the alpha helix and the left helix of the “polyproline II” type; alanine also stabilizes the beta structure in fibrillar proteins. The stabilizing effect of alanine on the structure of the alpha helix extends to both natively unfolded proteins and alpha helix–substrate conjugates. In short, it would not be an exaggeration to say that the problem of the formation of the secondary structure of protein is reduced to the problem of alanine. The revealed contradictions are paradoxical and their interpretation (first of all, the substantiation of the contribution of alanine to the enthalpy of melting in terms of fundamental physics) is currently absent. However, the data and comments presented in this paper inspire hope for progress in resolving thes contradictions.