Antibacterial Target DXP Synthase Catalyzes the Cleavage of d -Xylulose 5-Phosphate: a Study of Ketose Phosphate Binding and Ketol Transfer Reaction
| Autor: | Melanie L. Johnston, Eucolona M. Bonett, Alicia A. DeColli, Caren L. Freel Meyers |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Biochemistry. 61:1810-1823 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/acs.biochem.2c00274 |
| Popis: | The bacterial enzyme 1-deoxy-d-xylulose 5-phosphate synthase (DXPS) catalyzes the formation of DXP from pyruvate and d-glyceraldehyde 3-phosphate (d-GAP) in a thiamin diphosphate (ThDP)-dependent manner. In addition to its role in isoprenoid biosynthesis, DXP is required for ThDP and pyridoxal phosphate biosynthesis. Due to its function as a branch-point enzyme and its demonstrated substrate and catalytic promiscuity, we hypothesize that DXPS could be key for bacterial adaptation in the dynamic metabolic landscape during infection. Prior work in the Freel Meyers laboratory has illustrated that DXPS displays relaxed specificity toward donor and acceptor substrates and varies acceptor specificity according to the donor used. We have reported that DXPS forms dihydroxyethyl (DHE)ThDP from ketoacid or aldehyde donor substrates via decarboxylation and deprotonation, respectively. Here, we tested other DHE donors and found that DXPS cleaves d-xylulose 5-phosphate (X5P) at C2-C3, producing DHEThDP through a third mechanism involving d-GAP elimination. We interrogated DXPS-catalyzed reactions using X5P as a donor substrate and illustrated (1) production of a semi-stable enzyme-bound intermediate and (2) O |
| Databáze: | OpenAIRE |
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