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In the quest for new targets for pathogen eradication: the adenylosuccinate synthetase from the bacterium Helicobacter pylori
Authors:Ante Bubi?  Natalia Mrnjavac  Igor Stuparevi?  Marta ?yczek  Beata Wielgus-Kutrowska  Agnieszka Bzowska
Institution:1. Division of Physical Chemistry, Ru?er Bo?kovi? Institute, Zagreb, Croatia;2. Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia;3. Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, Poland;4. Department of Bacterial Genetics, Faculty of Biology, Institute of Microbiology, University of Warsaw, Warsaw, Poland
Abstract:Adenylosuccinate synthetase (AdSS) is an enzyme at regulatory point of purine metabolism. In pathogenic organisms which utilise only the purine salvage pathway, AdSS asserts itself as a promising drug target. One of these organisms is Helicobacter pylori, a wide-spread human pathogen involved in the development of many diseases. The rate of H. pylori antibiotic resistance is on the increase, making the quest for new drugs against this pathogen more important than ever. In this context, we describe here the properties of H. pylori AdSS. This enzyme exists in a dimeric active form independently of the presence of its ligands. Its narrow stability range and pH-neutral optimal working conditions reflect the bacterium’s high level of adaptation to its living environment. Efficient inhibition of H. pylori AdSS with hadacidin and adenylosuccinate gives hope of finding novel drugs that aim at eradicating this dangerous pathogen.
Keywords:Helicobacter pylori  adenylosuccinate synthetase  enzyme kinetics  enzyme inhibition  oligomeric state  analytical ultracentrifugation
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