Comparative Analyses of the β-Tubulin Gene and Molecular Modeling Reveal Molecular Insight into the Colchicine Resistance in Kinetoplastids Organisms
Figure 3
The conformation of the colchicine-binding domain on the -tubulin protein. (I) Comparison of the ribbon diagram of the crystallography model of the -tubulin protein of bovine (a) and the homology model of L. (V.) guyanensis (b). Secondary structure elements ( helix, -sheet, and coil) and the N and C terminal are marked. Overlay of both structures (yellow: bovine; blue: Leishmania) is presented (c). Arrow indicates the colchicine-binding domain; regions showing significant differences are marked (*). (II) Overview of the conformation of the colchicine-binding domain of the -tubulin protein of bovine (yellow) and Leishmania (blue). The ligands colchicine (CN2) bound to the domain and secondary structure elements associated with this region are presented and defined as follows: helix and sheet. The CN2 bound to the putative domain of Leishmania corresponds to a hypothetical representation to visualize the conformational changes in comparison with the bovine region. Superimposition of both structures is presented. (III) Amino acids residues substitutions and structural changes. The colchicine domains without ligands are the same as (II). The nonsynonymous mutation at positions 248 (1), 252 (2), 314 (3), and 352 (4), which generated change of nonpolar amino acid residues Ala (A), and the basic Lys (K) present in bovine to the polar one Ser (S) and nonpolar Met (M) in Leishmania are indicated. The side chain of particular amino acid residues, such as S and common amino acid residues Asn (256N) and Lys (350 K), embedded inside the Leishmania colchicine domain is presented on the superimposed of these structures, including CN2.
