Synthesis and Kinetic evaluation of an azido analogue of methylerythritol phosphate: a Novel Inhibitor of E. coli YgbP/IspD
| Autor: | Jean-Luc Ferrer, Philippe Chaignon, Alain Wagner, Franck Borel, Zoljargal Baatarkhuu, Myriam Seemann |
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| Přispěvatelé: | Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Strasbourg - Faculté de Médecine [Strabourg] (FMTS), Université Louis Pasteur - Strasbourg I-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-Institut de Chimie du CNRS (INC) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Plasmodium falciparum lcsh:Medicine Drug resistance [CHIM.THER]Chemical Sciences/Medicinal Chemistry medicine.disease_cause 01 natural sciences Article Phosphates 03 medical and health sciences chemistry.chemical_compound medicine Escherichia coli Humans Enzyme Inhibitors lcsh:Science chemistry.chemical_classification Multidisciplinary biology 010405 organic chemistry Escherichia coli Proteins lcsh:R Phosphate biology.organism_classification Antimicrobial Drug Resistance Multiple 3. Good health 0104 chemical sciences Multiple drug resistance Kinetics 030104 developmental biology Enzyme Erythritol chemistry Biochemistry Sugar Phosphates lcsh:Q Bacteria |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) Scientific Reports Scientific Reports, 2018, 8 (1), pp.17892. ⟨10.1038/s41598-018-35586-y⟩ Scientific Reports, Nature Publishing Group, 2018, 8 (1), pp.17892. ⟨10.1038/s41598-018-35586-y⟩ |
| ISSN: | 2045-2322 |
| Popis: | As multidrug resistant pathogenic microorganisms are a serious health menace, it is crucial to continuously develop novel medicines in order to overcome the emerging resistance. The methylerythritol phosphate pathway (MEP) is an ideal target for antimicrobial development as it is absent in humans but present in most bacteria and in the parasite Plasmodium falciparum. Here, we report the synthesis and the steady-state kinetics of a novel potent inhibitor (MEPN3) of Escherichia coli YgbP/IspD, the third enzyme of the MEP pathway. MEPN3 inhibits E. coli YgbP/IspD in mixed type mode regarding both substrates. Interestingly, MEPN3 shows the highest inhibitory activity when compared to known inhibitors of E. coli YgbP/IspD. The mechanism of this enzyme was also studied by steady-state kinetic analysis and it was found that the substrates add to the enzyme in sequential manner. |
| Databáze: | OpenAIRE |
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