Bacterial cell division is a complex process involving several proteins among which FtsZ, a prokaryotic homologue of tubulin, plays a central role. Prior to the onset of division or septation, FtsZ, a cytoplasmic protein, assembles at the middle of the cell into a dynamic ring-like structure (Z ring) and remains at the constricting edge of the septum until its completion. The Z ring acts as a scaffold and recruits other cell division proteins in a linear order to form the division machinery. In E. coli, the endogenous cell division inhibitors, SulA. and MinC prevent Z ring formation which is lethal to the cell. In vitro, both inhibitors block FtsZ polymerization. Thus FtsZ and the other cell division proteins are attractive targets for novel anti-microbials. The long term objective of this proposal is to develop new anti-microbials that target FtsZ and other cell division protein. FtsZ complexed with SuIA will be crystalized for structural studies. The information will give us a better understanding how FtsZ function can be blocked. High throughput assays for FtsZ GTPase and polymerization activities will also be developed to screen a library of natural compounds and a library derived by combinatorial chemistry. Finally, we will utilize the peptide aptamer technology to identify aptamers that target cell division proteins. We will also look for peptide aptamers that block growth arrest and identifying their targets could lead to discovery of novel targets for drug design.
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