Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains

Wojtyś, Marta Ilona; Maksymiuk, Weronika; Narczyk, Marta; Bubić, Ante; Leščić Ašler, Ivana; Krzyżek, Paweł; Gościniak, Grażyna; Jagusztyn-Krynicka, Elżbieta Katarzyna; Bzowska, Agnieszka (2024) Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains. Journal of Enzyme Inhibition and Medicinal Chemistry, 39 (1). ISSN 1475-6366

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Abstract

The current therapies against gastric pathogen Helicobacter pylori are ineffective in over 20% of patients. Enzymes belonging to the purine salvage pathway are considered as novel drug targets in this pathogen. Therefore, the main aim of the current study was to determine the antibacterial activity of pyridoxal 5’-phosphate (PLP), an active form of vitamin B6, against reference and clinical strains of H. pylori. Using a broad set of microbiological, physicochemical (UV absorption, LC-MS, X-ray analysis) and in silico experiments, we were able to prove that PLP inhibits adenylosuccinate synthetase (AdSS) from H. pylori by the competition with GTP (IC50eq ∼30 nM). This behaviour was attributed to formation of a Schiff base with a lysine residue (a covalent bond with Lys322 in the GTP binding site of AdSS) and was potentiated by the presence of vitamin C. This antibacterial activity of PLP gives hope for its future use against H. pylori.

Item Type:	Article
Uncontrolled Keywords:	Adenylosuccinate synthetase ; Helicobacter pylori ; vitamin B6 ; antimicrobial activity ; X-ray structure
Subjects:	NATURAL SCIENCES > Chemistry BIOMEDICINE AND HEALTHCARE > Pharmacy > Medical Biochemistry
Divisions:	Division of Physical Chemistry
Projects:	Project title Project leader Project code Project type Enzimi purinskog reciklirajućeg ciklusa iz Helicobacter pylori i Escherichie coli-PSPE Marija Luić IP-2013-11-7423 HRZZ Alosterički komunikacijski putevi u oligomernim enzimima-ALOKOMP/ALOCOMP Zoran Štefanić; Marko Tomin; Aleksandra Maršavelski; Alessandro Pandini; Bojana Dalbelo-Bašić; Agnieszka Bzowska IP-2019-04-6764 HRZZ
Depositing User:	Ivana Vuglec
Date Deposited:	25 Nov 2025 15:46
URI:	http://fulir.irb.hr/id/eprint/10089
DOI:	10.1080/14756366.2024.2372734

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