No abstract

The major part of commercial prodrugs against Mycobacterium tuberculosis (Mtb) demonstrated a significant inhibitory effect on cell division and inhibition of bacterial growth in vitro. However, further implementation often failed to overcome the compensatory system of interchangeable cascades. This is the most common situation for the compounds, which hit the key enzymes activities involved in all basic stages of the cell cycle. We decided to find more compounds, which could affect a cytoskeleton complex playing important role in sensing the external signals, intracellular transport, and cell division. In general, the bacterial cytoskeleton is crucial for response to the environment and participates in cell-to-cell communication. In turn, filamentous temperature-sensitive Z (FtsZ) protein, a mycobacterial tubulin homolog, is essential for Z-ring formation and further bacteria cell division. We predicted the most preferable binding-sites and conducted a highthroughput virtual screening. Modeling results suggest that some compounds bind in a specific region on the surface Mtb FtsZ, which is absent in human, and other could hit GTPase activity of the FtsZ. Further in vitro studies confirmed that these novel molecules can efficiently bind to these pockets, demonstrating an effect on the polymerization state and kinetics mechanisms.The rescaling of the experiment on the cell line revealed that reported

Plant systems have been considered valuable models for addressing fundamental questions of microtubule (MT) organization due to their considerable practical utility. Protein acetylation is a very common protein modification, and therate of acetylation can be modulated in cells in different biological states, and these changes can be detected at a molecular level. Here, we focused on K40, K112, and K394 residues as putative acetylation sites, which were shown to exist in both plants and mammals. Such residual effect of acetylation causes critical but unclear effect on MT stability. In turn, it was shown that acetylation indirectly affects the probability of interaction with different MAPs (Microtubule‐associated proteins). In a multiscale study using an all‐atom force field to reproduce several lattice‐forming elements found on the surface the microtubule, we assembled a fragment of a plant microtubule composed of nine tubulins and used it as a model object along with the existing human complex. Triplets of tubulins assembled in a lattice cell were then simulated for both human and plant protein complexes, using a coarse‐grained force field. We then analyzed the trajectories and identified some critical deformations of the MAP interaction surface. The initial coordinates were used to investigate the structural scenario in which autophagy‐related protein 8 (ATG8) was able to interact with the MT fragment.