The ParD-ParE system represents a toxin-antitoxin module of the broad host range plasmid RK2. ParE (103 amino acids) is the toxin, whereas ParD (83 amino acids) constitutes the antidote able to neutralize ParE by forming a stable complex that is also effective in the autorepression of the parDE operon. The ParE toxin inhibits DNA gyrase activity and thereby blocks DNA replication. Several studies have shown that ParD consists of two structurally distinct regions: an N-terminal, orderly, consisting of the DNA binding site and another C-terminus, unstructured, where it is suggested to occur toxin binding. For binding with toxin, a current model of recognition and binding in TA systems invokes a disorder-to-order transition in the antitoxin. Specifically, a disordered region of the free antitoxin is organized into a well-defined secondary structure upon binding to its cognate toxin. But, no available data that proves the application of disorder-to-order transition model for ParD-ParE system.Therefore, this work aims to study the interaction of the ParE protein and its analogues with peptides from ParD antitoxin. The idea is to find the minimal ParD structure able to neutralize the deleterious effect of ParE. Thus, will allow the design and the synthesis of new peptide sequences from ParE with a powerful interaction with ParD, so that intracellularly, may compete with the native protein for the more stable ParD complex formation, leaving ParE free for topoisomerases inhibition.The expectation is that the results may help identify the key points of interaction between ParE and ParD, as well as in the development of new inhibitors of bacterial topoisomerases that result in antibiotics with large antibacterial capacity, fewer tendencies to the emergence of resistance and reduced toxicity for eukaryotic cells.
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