Demchuk O. Analysis of the sequence homology of prokaryotic and eukaryotic FtsZ-proteins and structural-biological characteristics of the binding of benzimidazole compounds

The FtsZ-protein sequences of different origin were compared. E. coli FtsZ and A. thaliana cytosolic FtsZ-protein spatial structures were predicted. The 3D-models for these proteins suitable for molecular docking simulations were reconstructed. Molecular docking of 2-aryl-2,3-dihydro-4Н-[1,3]-thiazin-[3,2а]-benzimidazol-4-ones were performed. Accordingly to docking results, the benzimidazole binding site was specified. Based on in silico analysis of bacterial and plant FtsZ proteins to form complexes with range of benzimidazole derivatives, features of interaction and affinity levels were characterized. For the first time, in vitro interaction of E. coli FtsZ with aryl-thiazyne derivatives of benzimidazole was confirmed spectrophotometrically. The four compounds inhibiting E. coli FtsZ protofilament disassembly were identified. Similarity of spatial structures of E. coli and M. tuberculosis FtsZ-benzimidazole complexes was approved. The results of these studies are opening new opportunities for antituberculous application of studied compounds. Key words: Ftsz, benzimidazole derivatives, inhibitors, three-dimensional structure, binding site, molecular dynamics.