a Division of Physical Chemistry , Ruđer Bošković Institute , Zagreb , Croatia.
b Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology , University of Zagreb , Zagreb , Croatia.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):1405-1414. doi: 10.1080/14756366.2018.1506773.
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.
腺嘌呤琥珀酸合成酶(AdSS)是嘌呤代谢的调节点酶。在仅利用嘌呤补救途径的致病生物体中,AdSS 作为一个有前途的药物靶点。其中一种生物体是幽门螺杆菌,一种广泛存在的人类病原体,与许多疾病的发展有关。幽门螺杆菌对抗生素的耐药率正在上升,因此寻找针对这种病原体的新药比以往任何时候都更加重要。在这种情况下,我们在这里描述了幽门螺杆菌 AdSS 的特性。这种酶以二聚体的活性形式存在,而与其配体无关。其狭窄的稳定性范围和 pH 中性的最佳工作条件反映了细菌对其生存环境的高度适应。用哈地辛和腺嘌呤琥珀酸有效地抑制幽门螺杆菌 AdSS,为寻找旨在根除这种危险病原体的新型药物带来了希望。