[Comparative analysis of primary structure of the mutant tubulins with resistance to antimicrotubular drugs for prediction of new mutations with analogous properties]

Abstract

All known for today complete amino acid sequences of alpha- and beta-tubulins were aligned and analyzed to reveal the regularity of location of mutations result in the resistance to antimicrotubular compounds and a prediction of positions of new similar mutations. It was shown, that known positions of amino acid changes lead to decrease a affinity to antimicrotubular agents with depolymerizing mechanism of action are consensus and located in proximity to the residues involved in intradimeric/interdimeric interactions and interactions with nucleotides (within of six residues), but never coincide with them. For changes lead to resistance to stabilizing antimicrotubular compounds, similar dependence is not traced. The identified regularity enables to predict the positions of new mutations lead to resistance to agents with depolymerizing mechanism of action.