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In the quest for new targets for pathogen eradication: the adenylosuccinate synthetase from the bacterium Helicobacter pylori

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journal contribution
posted on 2018-09-07, 09:43 authored by Ante Bubić, Natalia Mrnjavac, Igor Stuparević, Marta Łyczek, Beata Wielgus-Kutrowska, Agnieszka Bzowska, Marija Luić, Ivana Leščić Ašler

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.

Funding

This research has been supported by the Croatian Science Foundation (project no. 7423) and by the project Harmonia 2015/18/M/NZ1/00776 granted by the National Science Centre of Poland, and by the Polish Ministry for Science and Higher Education grant BST-173300/BF.

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