Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains
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...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2024.2372734 |
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| author | Marta Ilona Wojtyś Weronika Maksymiuk Marta Narczyk Ante Bubić Ivana Leščić Ašler Paweł Krzyżek Grażyna Gościniak Elżbieta Katarzyna Jagusztyn-Krynicka Agnieszka Bzowska |
| author_facet | Marta Ilona Wojtyś Weronika Maksymiuk Marta Narczyk Ante Bubić Ivana Leščić Ašler Paweł Krzyżek Grażyna Gościniak Elżbieta Katarzyna Jagusztyn-Krynicka Agnieszka Bzowska |
| author_sort | Marta Ilona Wojtyś |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d49a28023d5d4282a32dff07929d534e |
| institution | Kabale University |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-d49a28023d5d4282a32dff07929d534e2024-12-26T09:30:43ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2372734Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strainsMarta Ilona Wojtyś0Weronika Maksymiuk1Marta Narczyk2Ante Bubić3Ivana Leščić Ašler4Paweł Krzyżek5Grażyna Gościniak6Elżbieta Katarzyna Jagusztyn-Krynicka7Agnieszka Bzowska8Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, PolandDivision of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, PolandDivision of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, PolandDivision of Physical Chemistry, Ruđer Bošković Institute, Zagreb, CroatiaDivision of Physical Chemistry, Ruđer Bošković Institute, Zagreb, CroatiaDepartment of Microbiology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, PolandDepartment of Microbiology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, PolandDepartment of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, PolandDivision of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, PolandThe 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.https://www.tandfonline.com/doi/10.1080/14756366.2024.2372734Adenylosuccinate synthetaseHelicobacter pylorivitamin B6antimicrobial activityX-ray structure |
| spellingShingle | Marta Ilona Wojtyś Weronika Maksymiuk Marta Narczyk Ante Bubić Ivana Leščić Ašler Paweł Krzyżek Grażyna Gościniak Elżbieta Katarzyna Jagusztyn-Krynicka Agnieszka Bzowska 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 Adenylosuccinate synthetase Helicobacter pylori vitamin B6 antimicrobial activity X-ray structure |
| title | Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains |
| title_full | Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains |
| title_fullStr | Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains |
| title_full_unstemmed | Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains |
| title_short | Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains |
| title_sort | vitamin b6 inhibits activity of helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical antibiotic resistant h pylori strains |
| topic | Adenylosuccinate synthetase Helicobacter pylori vitamin B6 antimicrobial activity X-ray structure |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2372734 |
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