title: Targeting the Bacterial Division Protein FtsZ.
abstract: Similar to its eukaryotic counterpart, the prokaryotic cytoskeleton is essential for the structural and mechanical properties of bacterial cells. The essential protein FtsZ is a central player in the cytoskeletal family, forms a cytokinetic ring at mid-cell, and recruits the division machinery to orchestrate cell division. Cells depleted of or lacking functional FtsZ do not divide and grow into long filaments that eventually lyse. FtsZ has been studied extensively as a target for antibacterial development. In this Perspective, we review the structural and biochemical properties of FtsZ, its role in cell biochemistry and physiology, the different mechanisms of inhibiting FtsZ, small molecule antagonists (including some misconceptions about mechanisms of action), and their discovery strategies. This collective information will inform chemists on different aspects of FtsZ that can be (and have been) used to develop successful strategies for devising new families of cell division inhibitors.
authors.affiliation: Department of Pharmaceutical Sciences, University of Wisconsin-Madison , 777 Highland Avenue, Madison, Wisconsin 53705, United States.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hurley
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison , 440 Henry Mall, Madison, Wisconsin 53706, United States.
authors.forename: Thiago M A
authors.initials: TM
authors.lastname: Santos
authors.affiliation: Department of Chemistry, University of California-Davis , One Shields Avenue, Davis, California 95616, United States.
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Nepomuceno
authors.affiliation: Department of Chemistry, University of California-Davis , One Shields Avenue, Davis, California 95616, United States.
authors.forename: Valerie
authors.initials: V
authors.lastname: Huynh
authors.affiliation: Department of Chemistry, University of California-Davis , One Shields Avenue, Davis, California 95616, United States.
authors.forename: Jared T
authors.initials: JT
authors.lastname: Shaw
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison , 440 Henry Mall, Madison, Wisconsin 53706, United States.|Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.|Department of Biomedical Engineering, University of Wisconsin-Madison , 1550 Engineering Drive, Madison, Wisconsin 53706, United States.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Weibel
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria