scholarly journals Creating an Antibacterial with in Vivo Efficacy: Synthesis and Characterization of Potent Inhibitors of the Bacterial Cell Division Protein FtsZ with Improved Pharmaceutical Properties

2010 ◽  
Vol 53 (10) ◽  
pp. 3927-3936 ◽  
Author(s):  
David J. Haydon ◽  
James M. Bennett ◽  
David Brown ◽  
Ian Collins ◽  
Greta Galbraith ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Synthesis And Characterization ◽  
Bacterial Cell Division ◽  
In Vivo Efficacy ◽  
Cell Division Protein ◽  
Pharmaceutical Properties

scholarly journals A conserved cell division protein directly regulates FtsZ dynamics in filamentous and unicellular actinobacteria

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Félix Ramos-León ◽  
Matthew J Bush ◽  
Joseph W Sallmen ◽  
Govind Chandra ◽  
Jake Richardson ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Mycobacterium Smegmatis ◽  
Bacterial Cell Division ◽  
Z Ring ◽  
Cell Division Protein ◽  
Ring Architecture ◽  
Contractile Structure

Bacterial cell division is driven by the polymerization of the GTPase FtsZ into a contractile structure, the so-called Z-ring. This essential process involves proteins that modulate FtsZ dynamics and hence the overall Z-ring architecture. Actinobacteria like Streptomyces and Mycobacterium lack known key FtsZ-regulators. Here we report the identification of SepH, a conserved actinobacterial protein that directly regulates FtsZ dynamics. We show that SepH is crucially involved in cell division in Streptomyces venezuelae and that it binds FtsZ via a conserved helix-turn-helix motif, stimulating the assembly of FtsZ protofilaments. Comparative in vitro studies using the SepH homolog from Mycobacterium smegmatis further reveal that SepH can also bundle FtsZ protofilaments, indicating an additional Z-ring stabilizing function in vivo. We propose that SepH plays a crucial role at the onset of cytokinesis in actinobacteria by promoting the assembly of FtsZ filaments into division-competent Z-rings that can go on to mediate septum synthesis.

scholarly journals In Vivo Imaging of a Bacterial Cell Division Protein Using a Protease-Assisted Small-Molecule Labeling Approach

ChemBioChem ◽  
2008 ◽  
Vol 9 (5) ◽  
pp. 677-680 ◽  
Author(s):  
Souvik Chattopadhaya ◽  
Farhana B. Abu Bakar ◽  
Rajavel Srinivasan ◽  
Shao. Q. Yao
Keyword(s):  
Cell Division ◽  
Small Molecule ◽  
In Vivo Imaging ◽  
Bacterial Cell ◽  
Bacterial Cell Division ◽  
Cell Division Protein ◽  
Labeling Approach

scholarly journals A conserved cell division protein directly regulates FtsZ dynamics in filamentous and unicellular actinobacteria

2020 ◽  
Author(s):  
Felix Ramos-Léon ◽  
Matthew J. Bush ◽  
Joseph W. Sallmen ◽  
Govind Chandra ◽  
Jake Richardson ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Crucial Role ◽  
Bacterial Cell Division ◽  
Z Ring ◽  
Cell Division Protein ◽  
Ring Architecture ◽  
Contractile Structure

AbstractBacterial cell division is driven by the polymerization of the GTPase FtsZ into a contractile structure, the so-called Z-ring. This essential process involves proteins that modulate FtsZ dynamics and hence the overall Z-ring architecture. Actinobacteria, like Streptomyces and Mycobacterium lack known key FtsZ-regulators. Here we report the identification of SepH, a conserved actinobacterial protein that directly regulates FtsZ dynamics. We show that SepH is crucially involved in cell division in Streptomyces and that it binds FtsZ via a conserved helix-turn-helix motif, stimulating the assembly of FtsZ protofilaments. Comparative in vitro studies using the SepH homolog from Mycobacterium further reveal that SepH can also bundle FtsZ protofilaments, indicating an additional Z-ring stabilizing function in vivo. We propose that SepH plays a crucial role at the onset of cytokinesis in actinobacteria by promoting the rapid assembly of FtsZ filaments into division-competent Z-rings that can go on to mediate septum synthesis.

scholarly journals The bacterial cell division protein fragment EFtsN binds to and activates the major peptidoglycan synthase PBP1b

2020 ◽  
Vol 295 (52) ◽  
pp. 18256-18265
Author(s):  
Adrien Boes ◽  
Frederic Kerff ◽  
Raphael Herman ◽  
Thierry Touze ◽  
Eefjan Breukink ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Binding Pocket ◽  
Nonpermissive Temperature ◽  
Multiprotein Complex ◽  
Bacterial Cell Division ◽  
Protein Fragment ◽  
Division Site ◽  
Cell Division Protein

Peptidoglycan (PG) is an essential constituent of the bacterial cell wall. During cell division, the machinery responsible for PG synthesis localizes mid-cell, at the septum, under the control of a multiprotein complex called the divisome. In Escherichia coli, septal PG synthesis and cell constriction rely on the accumulation of FtsN at the division site. Interestingly, a short sequence of FtsN (Leu75–Gln93, known as EFtsN) was shown to be essential and sufficient for its functioning in vivo, but what exactly this sequence is doing remained unknown. Here, we show that EFtsN binds specifically to the major PG synthase PBP1b and is sufficient to stimulate its biosynthetic glycosyltransferase (GTase) activity. We also report the crystal structure of PBP1b in complex with EFtsN, which demonstrates that EFtsN binds at the junction between the GTase and UB2H domains of PBP1b. Interestingly, mutations to two residues (R141A/R397A) within the EFtsN-binding pocket reduced the activation of PBP1b by FtsN but not by the lipoprotein LpoB. This mutant was unable to rescue the ΔponB-ponAts strain, which lacks PBP1b and has a thermosensitive PBP1a, at nonpermissive temperature and induced a mild cell-chaining phenotype and cell lysis. Altogether, the results show that EFtsN interacts with PBP1b and that this interaction plays a role in the activation of its GTase activity by FtsN, which may contribute to the overall septal PG synthesis and regulation during cell division.

scholarly journals Assembly of bacterial cell division protein FtsZ into dynamic biomolecular condensates

2021 ◽  
Vol 1868 (5) ◽  
pp. 118986 ◽  
Author(s):  
Miguel Ángel Robles-Ramos ◽  
Silvia Zorrilla ◽  
Carlos Alfonso ◽  
William Margolin ◽  
Germán Rivas ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Bacterial Cell Division ◽  
Cell Division Protein

scholarly journals Structural reorganization of the bacterial cell-division protein FtsZ fromStaphylococcus aureus

2012 ◽  
Vol 68 (9) ◽  
pp. 1175-1188 ◽  
Author(s):  
Takashi Matsui ◽  
Junji Yamane ◽  
Nobuyuki Mogi ◽  
Hiroto Yamaguchi ◽  
Hiroshi Takemoto ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Bacterial Cell Division ◽  
Structural Reorganization ◽  
Cell Division Protein

scholarly journals Lateral interactions between protofilaments of the bacterial tubulin homolog FtsZ are essential for cell division

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Fenghui Guan ◽  
Jiayu Yu ◽  
Jie Yu ◽  
Yang Liu ◽  
Ying Li ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Dynamic Structure ◽  
Living Cells ◽  
Lateral Interactions ◽  
Bacterial Cell Division ◽  
Z Ring ◽  
Crystallographic Structures ◽  
Order Structures

The prokaryotic tubulin homolog FtsZ polymerizes into protofilaments, which further assemble into higher-order structures at future division sites to form the Z-ring, a dynamic structure essential for bacterial cell division. The precise nature of interactions between FtsZ protofilaments that organize the Z-ring and their physiological significance remain enigmatic. In this study, we solved two crystallographic structures of a pair of FtsZ protofilaments, and demonstrated that they assemble in an antiparallel manner through the formation of two different inter-protofilament lateral interfaces. Our in vivo photocrosslinking studies confirmed that such lateral interactions occur in living cells, and disruption of the lateral interactions rendered cells unable to divide. The inherently weak lateral interactions enable FtsZ protofilaments to self-organize into a dynamic Z-ring. These results have fundamental implications for our understanding of bacterial cell division and for developing antibiotics that target this key process.

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