Alanine scanning of dinitroaniline/phosphorothioamidate site of α-tubulin in plasmodium species distributed in India

  • O. M. Demchuk
  • P. A. Karpov
  • A. V. Rayevsky
  • S. P. Ozheredov
  • S. I. Spivak
  • A. I. Yemets
  • Ya. B. Blume


Aim. Identification of amino acid residues participating in specific binding of dinitroaniline and phosphorothioamidate compounds with α-tubulin in Plasmodium falciparum. Methods. Protein structure modelling, protein structure optimization using molecular dynamics method, ligand-protein docking, alanine scanning mutagenesis. Results. Molecular docking of canonical compounds and alanine scanning mutagenesis, indicate two key (Arg2, Val250) and one minor (Glu3) residues involved in binding of both - dinitroaniline and phosphorothioamidate compounds. At the same time, it was revealed two minor residues (Asp251, Glu254) interacting only with some members of dinitroaniline grope. Conclusions. It was identified amino acid residues predetermining existence of joint site and similar interaction of α-tubulin with dinitroani-
line and phosphorothioamidate compounds in P. falciparum.

Keywords: malaria, Plasmodium, α-tubulin, molecular interaction, dinitroanilines compounds, phosphorothioamidate compounds, alanine scanning mutagenesis.


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