ArticleChembiochem : a European journal of chemical biology2015
Hydroxybenzaldoximes Are D-GAP-Competitive Inhibitors of E. coli 1-Deoxy-D-Xylulose-5-Phosphate Synthase.
Article in Chembiochem : a European journal of chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Aromatic Residues in Mobile Regions Distal to the Active Site Support the Closed Conformation ofBiochemistry · 2026Article
- 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
- 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
- Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo.Nature communications · 2023Article
- DXP Synthase Function in a Bacterial Metabolic Adaptation and Implications for Antibacterial Strategies.Antibiotics (Basel, Switzerland) · 2023Article
- The Multifaceted MEP Pathway: Towards New Therapeutic Perspectives.Molecules (Basel, Switzerland) · 2023Review
- 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
- Toward Understanding the Chemistry and Biology of 1-Deoxy-d-xylulose 5-Phosphate (DXP) Synthase: A Unique Antimicrobial Target at the Heart of Bacterial Metabolism.Accounts of chemical research · 2018Article
- Targeting the Unique Mechanism of Bacterial 1-Deoxy-d-xylulose-5-phosphate Synthase.Biochemistry · 2018Article
- Oxidative decarboxylation of pyruvate by 1-deoxy-d-xyulose 5-phosphate synthase, a central metabolic enzyme in bacteria.The Journal of biological chemistry · 2018Article
- Growth medium-dependent antimicrobial activity of early stage MEP pathway inhibitors.PloS one · 2018Article
- Conformational dynamics of 1-deoxy-d-xylulose 5-phosphate synthase on ligand binding revealed by H/D exchange MS.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Challenges and Hallmarks of Establishing Alkylacetylphosphonates as Probes of Bacterial 1-Deoxy-d-xylulose 5-Phosphate Synthase.ACS infectious diseases · 2017Article
- Mechanistic binding insights for 1-deoxy-D-Xylulose-5-Phosphate synthase, the enzyme catalyzing the first reaction of isoprenoid biosynthesis in the malaria-causing protists, Plasmodium falciparum and Plasmodium vivax.Protein expression and purification · 2016Article
- Competence of Thiamin Diphosphate-Dependent Enzymes with 2'-Methoxythiamin Diphosphate Derived from Bacimethrin, a Naturally Occurring Thiamin Anti-vitamin.Biochemistry · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
1-Deoxy-D-xylulose 5-phosphate (DXP) synthase is the first enzyme in the methylerythritol phosphate pathway to essential isoprenoids in pathogenic bacteria and apicomplexan parasites. In bacterial pathogens, DXP lies at a metabolic branch point, serving also as a precursor in the biosynthesis of vitamins B1 and B6, which are critical for central metabolism. In an effort to identify new bisubstrate analogue inhibitors that exploit the large active site and distinct mechanism of DXP synthase, a library of aryl mixed oximes was prepared and evaluated. Trihydroxybenzaldoximes emerged as reversible, low-micromolar inhibitors, competitive against D-glyceraldehyde 3-phosphate (D-GAP) and either uncompetitive or noncompetitive against pyruvate. Hydroxybenzaldoximes are the first class of D-GAP-competitive DXP synthase inhibitors, offering new tools for mechanistic studies of DXP synthase and a new direction for the development of antimicrobial agents targeting isoprenoid biosynthesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.