Exploration of the inhibitory mechanism of PC190723 on FtsZ protein by molecular dynamics simulation

Bacterial resistance caused by widespread use and abuse of antibiotics is threatening human health, and the development of new antibacterial agents with novel antibacterial targets has become urgent. Filamenting temperature-sensitive mutant Z (FtsZ), as a key protein in bacterial division, has received extensive attention. PC190723 exhibits an outstanding antibacterial activity by producing potent inhibitory ability on FtsZ protein, but its influence on the conformation of FtsZ protein at the molecular level is still unclear. In this study, we explored the effect of PC190723 on the conformation and function of FtsZ protein through molecular dynamics (MD) simulation and post-analysis. The results showed that PC190723 increased the high-affinity conformational stability of FtsZ protein, which disrupts the normal assembly of the Z-ring. In particular, the interactions of residues S8-sheet (VAL260-GLY266) increased in the FtsZPC190723 system, which may be the reason for promotes the formation of protofilament. In brief, the mechanism of PC190723 inhibiting FtsZ protein was explained at the molecular level by MD simulation, which provides new ideas for the identification of new FtsZ inhibitors as antibacterial agents. In this paper, the mechanism of PC190723 inhibiting FtsZ protein was explained at the molecular level by MD simulation, which provides new ideas for the identification of new FtsZ inhibitors as antibacterial agents. [Display omitted] •Benzamide group of PC190723 is the key group for inhibitory ability against FtsZ protein.•PC190723 enhanced the stability of FtsZ high-affinity conformation that would promote polymer assembly.•S8-sheet (VAL260-GLY266) may be the key residue region to promote the formation of protofilament.