Last update 01 Nov 2024

FtsZ

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction-

Drugs associated with FtsZ

FtsZ-targeting bactericidal agent(TAXIS)

Target

FtsZ

Mechanism

FtsZ inhibitors

Active Org.

TAXIS Pharmaceuticals, Inc.

Originator Org.

TAXIS Pharmaceuticals, Inc.

Active Indication

Bacterial Infections

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SB-P8B2

Target

FtsZ

Mechanism

FtsZ inhibitors

Active Org.

Stony Brook University

Originator Org.

Stony Brook University

Active Indication

Tuberculosis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TXY541

Target

FtsZ

Mechanism

FtsZ inhibitors

Active Org.

TAXIS Pharmaceuticals, Inc.

Originator Org.

TAXIS Pharmaceuticals, Inc.

Active Indication

Staphylococcal Infections

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with FtsZ

100 Translational Medicine associated with FtsZ

0 Patents (Medical) associated with FtsZ

2,540

Literatures (Medical) associated with FtsZ

01 Dec 2024·Biochemical Pharmacology

Recent advances in studies on FtsZ inhibitors

Review

Author: Lu, Bin ; Liu, Lan-Tian ; Yao, Chun-Meng ; Hou, Bo ; Wang, Xu-Fang ; Wang, Yan-Ting

With the abuse of antibiotics, multidrug resistant strains continue to emerge and spread rapidly. Therefore, there is an urgent need to develop new antimicrobial drugs. As a highly conserved cell division protein in bacteria, filamenting temperature-sensitive mutant Z (FtsZ) has been identified as a potential antimicrobial target. This paper reviews the structure, function, and action mechanism of FtsZ and a variety of natural and synthetic compounds targeting FtsZ, including 3-MBA derivatives, taxane derivatives, cinnamaldehyde, curcumin, quinoline and quinazoline derivatives, aromatic compounds, purpurin, and totarol. From these studies, FtsZ has a clear supporting role in the field of antimicrobial drug discovery. The urgent need and interest of antibacterial drugs will contribute to the discovery of new clinical drugs targeting FtsZ.

01 Nov 2024·International Journal of Biological Macromolecules

Staphylococcus aureus major cell division protein FtsZ assembly is inhibited by silibinin, a natural flavonolignan that also blocked bacterial growth and biofilm formation

Article

Author: Basak, Prithvi ; Sau, Subrata ; Ghosh, Dipanjan ; Dastidar, Debabrata Ghosh ; Chakraborty, Tushar ; Chakrabarti, Gopal

The bacterial cell division protein FtsZ has been considered a potential therapeutic target due to its rapid treadmilling that induces cellular wall construction in bacteria. The current study discovered a novel antimicrobial compound, silibinin, a natural flavonolignan and its impact on the recombinant S. aureus FtsZ (SaFtsZ). Silibinin inhibited S. aureus Newman growth in a dose-dependent manner. The IC₅₀ and MIC values for silibinin were 75 μM and 200 μM, respectively. It had no cytotoxicity against HEK293 cells in vitro. Silibinin also enlarged the bacterial cell morphology by ∼40 folds and showed antibiofilm property. It perturbed the S. aureus membrane potential both at IC₅₀ conc. and at MIC conc. Further, it inhibited both the polymerization and GTPase activity of SaFtsZ. It did not inhibit tubulin assembly, a eukaryotic FtsZ homolog. A fluorescence quenching study yielded the K_d value for SaFtsZ-Silibinin interaction and binding stoichiometry 0.857 ± 0.188 μM and 1:1, respectively. Both in silico study and competition assay indicated that silibinin binds at the GTP binding site on SaFtsZ. The K_i value for the silibinin-mediated inhibition of SaFtsZ was 8.8 μM. Therefore, these findings have comprehensively shown the antimicrobial behavior of silibinin on S. aureus Newman cells targeting SaFtsZ.

24 Oct 2024·Journal of Bacteriology

The cell division protein FzlA performs a conserved function in diverse alphaproteobacteria

Article

Author: Aubry, Brody ; Payne, Isaac P. ; Brown, Pamela J. B. ; Goley, Erin D. ; Barrows, Jordan M.

ABSTRACT In almost all bacteria, the tubulin-like GTPase FtsZ polymerizes to form a “Z-ring” that marks the site of division. FtsZ recruits other proteins, collectively known as the divisome, that together remodel and constrict the envelope. Constriction is driven by peptidoglycan (PG) cell wall synthesis by the glycosyltransferase FtsW and the transpeptidase FtsI (FtsWI), but these enzymes require activation to function. How recruitment of FtsZ to the division site leads to FtsWI activation and constriction remains largely unknown. Previous work in our laboratory demonstrated that an FtsZ-binding protein, FzlA, is essential for activation of FtsWI in the alphaproteobacterium Caulobacter crescentus . Additionally, we found that FzlA binds to a DNA translocase called FtsK, suggesting that it may link constriction activation to chromosome segregation. FzlA is conserved throughout Alphaproteobacteria but has only been examined in detail in C. crescentus . Here, we explored whether FzlA function is conserved in diverse Alphaproteobacteria. We assessed FzlA homologs from Rickettsia parkeri and Agrobacterium tumefaciens , and found that, similar to C. crescentus FzlA, they bind directly to FtsZ and localize to midcell. The FtsZ-FzlA interaction interface is conserved, as we demonstrated that FzlA from each of the three species examined can bind to FtsZ from any of the three in vitro . Finally, we determined that A. tumefaciens FzlA can fulfill the essential function of FzlA when produced in C. crescentus , indicating conservation of function. These results suggest that FzlA serves as an important regulator that coordinates chromosome segregation with envelope constriction across diverse Alphaproteobacteria. IMPORTANCE Cell division is essential for bacterial replication and must be highly regulated to ensure robust remodeling of the cell wall in coordination with segregation of the genome to daughter cells. In Caulobacter crescentus , FzlA plays a major role in regulating this process by activating cell wall synthesis in a manner that couples constriction to chromosome segregation. FzlA is broadly conserved in Alphaproteobacteria, suggesting that it plays a similar function across this class of bacteria. Here, we have shown that, indeed, FzlA biochemical interactions and function are conserved in diverse Alphaproteobacteria. Because FzlA is conserved in Alphaproteobacterial human pathogens, understanding this protein and its interactome could present therapeutic benefits by identifying potential antibiotic targets to treat infections.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

FtsZ

Basic Info

Related

Analysis