The drug ornidazole inhibits photosynthesis in a different mechanism described for protozoa and anaerobic bacteria
| Autor: | Michael Gurevitz, Raanan Carmieli, Yehouda Marcus, Noam Tal, Mordechai Ronen |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0106 biological sciences
0301 basic medicine Dehydrogenase Cyanobacteria Photosynthesis Models Biological 01 natural sciences Biochemistry Bacteria Anaerobic 03 medical and health sciences Metronidazole medicine Molecular Biology Glyceraldehyde 3-phosphate dehydrogenase Ferredoxin chemistry.chemical_classification biology Ornidazole Synechocystis Glyceraldehyde-3-Phosphate Dehydrogenases Cell Biology Electron transport chain 030104 developmental biology Enzyme chemistry Trichomonas biology.protein Ferredoxins Anaerobic bacteria Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) Glycolysis Triose-Phosphate Isomerase 010606 plant biology & botany medicine.drug |
| Zdroj: | Biochemical Journal. 473:4413-4426 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bcj20160433 |
| Popis: | Ornidazole of the 5-nitroimidazole drug family is used to treat protozoan and anaerobic bacterial infections via a mechanism that involves preactivation by reduction of the nitro group, and production of toxic derivatives and radicals. Metronidazole, another drug family member, has been suggested to affect photosynthesis by draining electrons from the electron carrier ferredoxin, thus inhibiting NADP+ reduction and stimulating radical and peroxide production. Here we show, however, that ornidazole inhibits photosynthesis via a different mechanism. While having a minute effect on the photosynthetic electron transport and oxygen photoreduction, ornidazole hinders the activity of two Calvin cycle enzymes, triose-phosphate isomerase (TPI) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Modeling of ornidazole's interaction with ferredoxin of the protozoan Trichomonas suggests efficient electron tunneling from the iron–sulfur cluster to the nitro group of the drug. A similar docking site of ornidazole at the plant-type ferredoxin does not exist, and the best simulated alternative does not support such efficient tunneling. Notably, TPI was inhibited by ornidazole in the dark or when electron transport was blocked by dichloromethyl diphenylurea, indicating that this inhibition was unrelated to the electron transport machinery. Although TPI and GAPDH isoenzymes are involved in glycolysis and gluconeogenesis, ornidazole's effect on respiration of photoautotrophs is moderate, thus raising its value as an efficient inhibitor of photosynthesis. The scarcity of Calvin cycle inhibitors capable of penetrating cell membranes emphasizes on the value of ornidazole for studying the regulation of this cycle. |
| Databáze: | OpenAIRE |
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