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PcrA/UvrD/Rep DNA helicases in bacterial genomes
Authors:Patrick Chène
Institution:Druggability-Enzymology-Profiling Unit, Oncology Research, Novartis Institutes for BioMedical Research, WKL125 442, Novartis, CH-4002 Basel, Switzerland
Abstract:Helicases, which utilize the energy liberated by the hydrolysis of nucleotides to unwind nucleic acids, are involved in many aspects of nucleic acid metabolism. Various DNA helicases from the PcrA/UvrD/Rep subfamily are essential for the survival of different pathogenic bacteria and we have recently shown that they can be inhibited with small synthetic molecules. Altogether this suggests that these enzymes are potential new drug targets. Since little is known about the presence of these enzymes in bacterial genomes, 99 bacterial genomes were analyzed in the present study. This analysis reveals which and how many of these enzymes are found in bacteria, but more important, it identifies several of these enzymes as potential drug target candidates. In addition, this work identifies several proteins, called here PURL, that have a high homology with the PcrA/UvrD/Rep proteins and that may form an additional group in this helicase subfamily.
Keywords:PcrA  UvrD  Rep  DNA helicases  PURL  Drug discovery
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