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

Bubić, Ante; Mrnjavac, Natalia; Stuparević, Igor; Łyczek, Marta; Wielgus-Kutrowska, Beata; Bzowska, Agnieszka; Luić, Marija; Leščić Ašler, Ivana (2018) In the quest for new targets for pathogen eradication: the adenylosuccinate synthetase from the bacterium Helicobacter pylori. Journal of Enzyme Inhibition and Medicinal Chemistry, 33 (1). pp. 1405-1414. ISSN 1475-6366

Preview

PDF - Published Version - article
Available under License Creative Commons Attribution.
Download (1MB) | Preview

Official URL: https://www.tandfonline.com/doi/full/10.1080/14756...

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.

Item Type:

Article

Uncontrolled Keywords:

Helicobacter pylori ; adenylosuccinate synthetase ; enzyme kinetics ; enzyme inhibition ; oligomeric state ; analytical ultracentrifugation

Subjects:

NATURAL SCIENCES > Chemistry

Divisions:

Division of Physical Chemistry

Projects: