Structural mechanisms of interaction of cyanolcrylates with plant tubulin

The structural mechanisms underlying the specific binding of cyanoacrylate compounds with tubulin of higher plants have been studied by the example of the interaction of ethyl-(2Z)-3-amino-2-cyano-4-ethylhex-2-enoate (CA1) and isopropyl-(2Z)-3-amino-2-cyano-4-ethylhex-2-enoate (CA2) with Arabidopsis thaliana alpha-tubulin. It was revealed that the cyano group of cyanoacrylates is a functional analogue of the nitrile group, which determines the processes of specific interaction with plant tubulin for dinitroaniline compounds. Based on data on spatial structure fluctuations, the dynamics of hydrogen bonds and the interaction energy of CA1 and CA2 (the most probable binding mode for these compounds with plant alpha-tubulin) was identified and the appropriate site of interaction was characterized. Seven out of ten residues composing this site (Gln-133, Asn-249, Val-250, Asp-251, Val-252, Asn-253, and Glu-254) are obligatory components of dinitroanilines' binding site on the plant alpha-tubulin surface. Thus, the binding site on the alpha-tubulin surface characterized by us is able to recognize and specifically bind substances, which are cardinally different by their chemical nature and have no common pharmacophore groups, under the condition of a certain similarity of their electrostatic topology.