Bacterial cell division proteins as antibiotic targets

•PBP1B crystal structure access inhibition of its GTase activity.•Inhibition of FtsZ polymerization cures mice from Staphylococcusaureus infection.•FtsW and MraY activity assays and structures enable development of inhibitors.•FtsQLB surface interaction studies enable search for inhibitors of this i...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Bioorganic chemistry 2014-08, Vol.55, p.27-38
Hauptverfasser: den Blaauwen, Tanneke, Andreu, José M., Monasterio, Octavio
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:•PBP1B crystal structure access inhibition of its GTase activity.•Inhibition of FtsZ polymerization cures mice from Staphylococcusaureus infection.•FtsW and MraY activity assays and structures enable development of inhibitors.•FtsQLB surface interaction studies enable search for inhibitors of this interaction.•In cell screening assays based on specific targets are needed. Proteins involved in bacterial cell division often do not have a counterpart in eukaryotic cells and they are essential for the survival of the bacteria. The genetic accessibility of many bacterial species in combination with the Green Fluorescence Protein revolution to study localization of proteins and the availability of crystal structures has increased our knowledge on bacterial cell division considerably in this century. Consequently, bacterial cell division proteins are more and more recognized as potential new antibiotic targets. An international effort to find small molecules that inhibit the cell division initiating protein FtsZ has yielded many compounds of which some are promising as leads for preclinical use. The essential transglycosylase activity of peptidoglycan synthases has recently become accessible to inhibitor screening. Enzymatic assays for and structural information on essential integral membrane proteins such as MraY and FtsW involved in lipid II (the peptidoglycan building block precursor) biosynthesis have put these proteins on the list of potential new targets. This review summarises and discusses the results and approaches to the development of lead compounds that inhibit bacterial cell division.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2014.03.007