Comparative analysis of allosteric rearrangements in FtsZ protein structure induced by benzamide and 4-hydroxycoumarine compounds

Abstract

Aim. To reveal allosteric rearrangements of FtsZ molecules arising under the influence of benzamide compounds and 4-hydroxycoumarin derivatives. To discover the key molecular mechanisms predetermining the effect of the specified compounds on the cell division in bacteria. Methods. Comparative analysis of FtsZ protein structures and their complexes with ligands. Application of structural bioinformatics software for molecular visualization, measurement of interatomic distances and approximation of intramolecular shifts based on RMSD indicators. Results. Revealed conformational changes in FtsZ protein molecules, induced by allosteric effectors: 4-hydroxycoumarin – 4HC and benzamide – 9PC (PC-190723). Allosteric deformations and their consequences for intact FtsZ protein molecules, there GTPase domains, H7 helixes and C-terminal domains were studied. Conclusions. It was clarified that the binding of benzamides causes more significant shifts in the structure of the FtsZ protein monomer, its C-terminal domain, and H7 helix. At the same time, 4-hydroxycoumarins deform the structure of the GTPase domain almost twofold effectively. Both classes of compounds prosses allosteric action through unique mechanisms that are largely realized through deformations and displacements of the H7 helix. Despite the fact that these compounds demonstrate different allosteric mechanisms of action, their final effect can be summarized to destructions in GTP pocket, protofilament interfaces and the general geometry of molecule.