ArticleChembiochem : a European journal of chemical biology2013
DXP synthase-catalyzed C-N bond formation: nitroso substrate specificity studies guide selective inhibitor design.
Article in Chembiochem : a European journal of chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Differential Hydroxypyruvate Processing byBiochemistry · 2026Article
- Aromatic Residues in Mobile Regions Distal to the Active Site Support the Closed Conformation ofBiochemistry · 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
- Investigating inhibitors of 1-deoxy-d-xylulose 5-phosphate synthase in a mouse model of UTI.Microbiology spectrum · 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
- DXP Synthase Function in a Bacterial Metabolic Adaptation and Implications for Antibacterial Strategies.Antibiotics (Basel, Switzerland) · 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
- First crystal structures of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Mycobacterium tuberculosis indicate a distinct mechanism of intermediate stabilization.Scientific reports · 2022Article
- Revealing Donor Substrate-Dependent Mechanistic Control on DXPS, an Enzyme in Bacterial Central Metabolism.Biochemistry · 2021Article
- Excavating the functionally crucial active-site residues of the DXS protein of Bacillus subtilis by exploring its closest homologues.Journal, genetic engineering & biotechnology · 2020Article
- Active Site Histidines Link Conformational Dynamics with Catalysis on Anti-Infective Target 1-Deoxy-d-xylulose 5-Phosphate Synthase.Biochemistry · 2019Article
- X-ray crystallography-based structural elucidation of enzyme-bound intermediates along the 1-deoxy-d-xylulose 5-phosphate synthase reaction coordinate.The Journal of biological chemistry · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
1-Deoxy-D-xylulose 5-phosphate (DXP) synthase catalyzes the first step in the nonmammalian isoprenoid biosynthetic pathway to form DXP from pyruvate and D-glyceraldehyde 3-phosphate (D-GAP) in a thiamin diphosphate-dependent manner. Its unique structure and mechanism distinguish DXP synthase from its homologues and suggest that it should be pursued as an anti-infective drug target. However, few reports describe any development of selective inhibitors of this enzyme. Here, we reveal that DXP synthase catalyzes C-N bond formation and exploit aromatic nitroso substrates as active site probes. Substrate specificity studies reveal a high affinity of DXP synthase for aromatic nitroso substrates compared to the related ThDP-dependent enzyme pyruvate dehydrogenase (PDH). Results from inhibition and mutagenesis studies indicate that nitroso substrates bind to E. coli DXP synthase in a manner distinct from that of D-GAP. Our results suggest that the incorporation of aryl acceptor substrate mimics into unnatural bisubstrate analogues will impart selectivity to DXP synthase inhibitors. As a proof of concept, we show selective inhibition of DXP synthase by benzylacetylphosphonate (BnAP).
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