ArticleJournal of the American Chemical Society2012
Observation of thiamin-bound intermediates and microscopic rate constants for their interconversion on 1-deoxy-D-xylulose 5-phosphate synthase: 600-fold rate acceleration of pyruvate decarboxylation by D-glyceraldehyde-3-phosphate.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 69 citations in OpenAlex.
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- Leveraging a synthetic biology approach to enhance BCG-mediated expansion of Vγ9Vδ2 T cells.PloS one · 2026Article
- Aromatic residues in mobile regions distal to the active site support the closed conformation ofbioRxiv : the preprint server for biology · 2025Article
- Exploring the antimicrobial activity of pantothenamides against uropathogenicMicrobiology spectrum · 2025Article
- Trihydroxybenzaldoximes are Redox Cycling Inhibitors of ThDP-Dependent DXP Synthase.ACS chemical biology · 2025Article
- Trihydroxybenzaldoximes are redox cycling inhibitors of ThDP-dependent DXP synthase.bioRxiv : the preprint server for biology · 2025Article
- Bisubstrate Analog Inhibitors of DXP Synthase Show Species Specificity.Biochemistry · 2025Article
- Aldehyde-based Activation of C2α-lactylthiamin Diphosphate Decarboxylation on Bacterial 1-deoxy-d-xylulose 5-phosphate Synthase.Chembiochem : a European journal of chemical biology · 2024Article
- Evaluation of ketoclomazone and its analogues as inhibitors of 1-deoxy-d-xylulose 5-phosphate synthases and other thiamine diphosphate (ThDP)-dependent enzymes.RSC medicinal chemistry · 2024Article
- Potent Inhibition ofACS infectious diseases · 2024Article
- Disruption of an Active Site Network Leads to Activation of C2α-Lactylthiamin Diphosphate on the Antibacterial Target 1-Deoxy-d-xylulose-5-phosphate Synthase.Biochemistry · 2024Article
- An activity-based probe for antimicrobial target DXP synthase, a thiamin diphosphate-dependent enzyme.Frontiers in chemical biology · 2024Article
- MEP pathway products allosterically promote monomerization of deoxy-D-xylulose-5-phosphate synthase to feedback-regulate their supply.Plant communications · 2023Article
- Antibacterial Target DXP Synthase Catalyzes the Cleavage of d-Xylulose 5-Phosphate: a Study of Ketose Phosphate Binding and Ketol Transfer Reaction.Biochemistry · 2022Article
- YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway ofInternational journal of molecular sciences · 2022Article
- Positioning Bacillus subtilis as terpenoid cell factory.Journal of applied microbiology · 2021Review
- Hit-optimization using target-directed dynamic combinatorial chemistry: development of inhibitors of the anti-infective target 1-deoxy-d-xylulose-5-phosphate synthase.Chemical science · 2021Article
- Revealing Donor Substrate-Dependent Mechanistic Control on DXPS, an Enzyme in Bacterial Central Metabolism.Biochemistry · 2021Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The thiamin diphosphate (ThDP)-dependent enzyme 1-deoxy-D-xylulose 5-phosphate (DXP) synthase carries out the condensation of pyruvate as a 2-hydroxyethyl donor with d-glyceraldehyde-3-phosphate (d-GAP) as acceptor forming DXP. Toward understanding catalysis of this potential anti-infective drug target, we examined the pathway of the enzyme using steady state and presteady state kinetic methods. It was found that DXP synthase stabilizes the ThDP-bound predecarboxylation intermediate formed between ThDP and pyruvate (C2α-lactylThDP or LThDP) in the absence of D-GAP, while addition of D-GAP enhanced the rate of decarboxylation by at least 600-fold. We postulate that decarboxylation requires formation of a ternary complex with both LThDP and D-GAP bound, and the central enzyme-bound enamine reacts with D-GAP to form DXP. This appears to be the first study of a ThDP enzyme where the individual rate constants could be evaluated by time-resolved circular dichroism spectroscopy, and the results could have relevance to other ThDP enzymes in which decarboxylation is coupled to a ligation reaction. The acceleration of the rate of decarboxylation of enzyme-bound LThDP in the presence of D-GAP suggests a new approach to inhibitor design.
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