ArticleAntimicrobial agents and chemotherapy2001
Drug targeting Mycobacterium tuberculosis cell wall synthesis: genetics of dTDP-rhamnose synthetic enzymes and development of a microtiter plate-based screen for inhibitors of conversion of dTDP-glucose to dTDP-rhamnose.
Article in Antimicrobial agents and chemotherapy, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 150 citations in OpenAlex.
- Genome-wide transcriptional landscape ofFrontiers in immunology · 2026Article
- Proteomic insight into soybean response to flooding stress reveals changes in energy metabolism and cell wall modifications.PloS one · 2022Article
- Article
- Two RmlC homologs catalyze dTDP-4-keto-6-deoxy-D-glucose epimerization in Pseudomonas putida KT2440.Scientific reports · 2021Article
- Article
- Pangenome Analysis ofAntibiotics (Basel, Switzerland) · 2020Article
- Rhamnose Binding Protein as an Anti-Bacterial Agent-Targeting Biofilm ofMarine drugs · 2019Article
- Discovery of an RmlC/D fusion protein in the microalgaThe Journal of biological chemistry · 2019Article
- Streptococcal dTDP-L-rhamnose biosynthesis enzymes: functional characterization and lead compound identification.Molecular microbiology · 2019Article
- The Mycobacterium tuberculosis complex has a pathway for the biosynthesis of 4-formamido-4,6-dideoxy-d-glucose.Protein science : a publication of the Protein Society · 2018Article
- Disruption of the GDP-mannose synthesis pathway in Streptomyces coelicolor results in antibiotic hyper-susceptible phenotypes.Microbiology (Reading, England) · 2018Article
- The structure of glucose-1-phosphate thymidylyltransferase from Mycobacterium tuberculosis reveals the location of an essential magnesium ion in the RmlA-type enzymes.Protein science : a publication of the Protein Society · 2018Article
- Cyclic di-GMP regulates Mycobacterium tuberculosis resistance to ethionamide.Scientific reports · 2017Article
- The Production and Utilization of GDP-glucose in the Biosynthesis of Trehalose 6-Phosphate by Streptomyces venezuelae.The Journal of biological chemistry · 2017Article
- Rv3634c from Mycobacterium tuberculosis H37Rv encodes an enzyme with UDP-Gal/Glc and UDP-GalNAc 4-epimerase activities.PloS one · 2017Article
- Bacterial glycobiology: rhamnose-containing cell wall polysaccharides in Gram-positive bacteria.FEMS microbiology reviews · 2016Review
- Inhibition of Mycobacterium-RmlA by Molecular Modeling, Dynamics Simulation, and Docking.Advances in bioinformatics · 2016Article
- Computational evaluation of phytocompounds for combating drug resistant tuberculosis by multi-targeted therapy.Journal of molecular modeling · 2015Article
- Carbohydrates: Translation from sticky to sweet.Nature chemical biology · 2015Article
- The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan.Cold Spring Harbor perspectives in medicine · 2015Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
An L-rhamnosyl residue plays an essential structural role in the cell wall of Mycobacterium tuberculosis. Therefore, the four enzymes (RmlA to RmlD) that form dTDP-rhamnose from dTTP and glucose-1-phosphate are important targets for the development of new tuberculosis therapeutics. M. tuberculosis genes encoding RmlA, RmlC, and RmlD have been identified and expressed in Escherichia coli. It is shown here that genes for only one isotype each of RmlA to RmlD are present in the M. tuberculosis genome. The gene for RmlB is Rv3464. Rv3264c was shown to encode ManB, not a second isotype of RmlA. Using recombinant RmlB, -C, and -D enzymes, a microtiter plate assay was developed to screen for inhibitors of the formation of dTDP-rhamnose. The three enzymes were incubated with dTDP-glucose and NADPH to form dTDP-rhamnose and NADP(+) with a concomitant decrease in optical density at 340 nm (OD(340)). Inhibitor candidates were monitored for their ability to lower the rate of OD(340) change. To test the robustness and practicality of the assay, a chemical library of 8,000 compounds was screened. Eleven inhibitors active at 10 microM were identified; four of these showed activities against whole M. tuberculosis cells, with MICs from 128 to 16 microg/ml. A rhodanine structural motif was present in three of the enzyme inhibitors, and two of these showed activity against whole M. tuberculosis cells. The enzyme assay was used to screen 60 Peruvian plant extracts known to inhibit the growth of M. tuberculosis in culture; two extracts were active inhibitors in the enzyme assay at concentrations of less than 2 microg/ml.
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