Inhibition der bakteriellen RNA-basierten Ribonuklease P und Untersuchungen zum Reaktionsmechanismus der Protein-basierten Ribonuklease P aus Arabidopsis thaliana

Bacterial Ribonuclease P (RNase P), which is responsible for the 5’-maturation of precursor tRNAs (pre-tRNA), appears as a very interesting biomolecule. It is a ribozyme that consists of a catalytic RNA and a small auxiliary protein subunit. Moreover, bacterial RNase P differs substantially from RNase P enzymes of the two other domains of life, Archaea and Eukarya, which have recruited multiple protein components during evolution with a concomitant loss of robust RNA-alone activity. In addition, RNase P enzymes that are singular proteins lacking any RNA component have been identified in four of the five eukaryal supergroups. In human, two different RNase P enzymes coexist. The nuclear RNase P contains an RNA component and ten protein subunits, while the mitochondrial RNase P consists of a ternary protein complex devoid of any RNA component. These architectural differences combined with the fact that bacterial RNase P is indispensable for cell survival make the bacterial enzyme a promising target for the development of novel antibiotics. Since no antibiotics are yet known that bind to RNase P as the primary target, inhibitors of bacterial RNase P would open up novel perspectives to combat multiresistant bacterial pathogens.