Nature of the charge distribution in proteins.

Abstract

The significance of the fairly strong electric fields produced by the electric macrodipole of the α-helix and by ionic charges in stabilizing globular proteins has been recognized for some years1–4. These electrostatic interactions are involved at the active sites of functional proteins in binding a substrate or a coenzyme, or in enhancing enzymatic reaction rates2–5, and are unique among the many interactions affecting protein structure and function because of their long range, extending over the whole protein molecule. We have now analysed the distribution of the distances separating the ionic charges (ionized groups and the apparent charges at the termini of the α-helices) for more than 44,000 charge pairs in 14 proteins. Our results show that charges in the proteins are, on average, surrounded by charges of opposite sign. Previous calculation of the electric potential near the helix termini has shown that the electrostatic effect of the α-helix dipole is equivalent to the effect of one-half of a positive unit charge at the N-terminus of the α-helix and one-half of a negative unit charge at the C-terminus3. We report here that the macrodipole of the α-helix has the same order of contribution to stabilizing the native protein conformation as ionized groups.