De Leon GP, Elowe NH, Koteva KP, Valvano MA, Wright GD An In Vitro Screen of Bacterial Lipopolysaccharide Biosynthetic Enzymes Identifies an Inhibitor of ADP-Heptose Biosynthesis Chemistry and Biology13(4) (2006)
437-441
NCBI PubMed ID:16632256 Journal NLM ID:9500160 Publisher: Maryland Heights, MO: Elsevier Correspondence: wrightgemcmaster.ca Institutions: Antimicrobial Research Centre Department of Biochemistry and Biomedical Sciences McMaster University Hamilton, Hamilton, ON, Canada, Infectious Diseases Research Group Siebens-Drake Research Institute Department of Microbiology and Immunology The University of Western Ontario London, Ontario N6A 5C1 Canada
The lipopolysaccharide (LPS)-rich outer membrane of gram-negative bacteria provides a protective barrier that insulates these organisms from the action of numerous antibiotics. Breach of the LPS layer can therefore provide access to the cell interior to otherwise impermeant toxic molecules and can expose vulnerable binding sites for immune system components such as complement. Inhibition of LPS biosynthesis, leading to a truncated LPS molecule, is an alternative strategy for antibacterial drug development in which this vital cellular structure is weakened. A significant challenge for in vitro screens of small molecules for inhibition of LPS biosynthesis is the difficulty in accessing the complex carbohydrate substrates. We have optimized an assay of the enzymes required for LPS heptose biosynthesis that simultaneously surveys five enzyme activities by using commercially available substrates and report its use in a small-molecule screen that identifies an inhibitor of heptose synthesis
Methods: biochemical methods Biosynthesis and genetic data: biosynthesis data
Related record ID(s): 10551, 20124, 20418, 20420, 20421, 20422, 20429, 23425 NCBI Taxonomy refs (TaxIDs):562 Reference(s) to other database(s): GTC:G37889CH, GlycomeDB:27767 Show glycosyltransferases
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