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Antibacterial activity of 2-amino-4-hydroxypyrimidine-5-carboxylates and binding to Burkholderia pseudomallei 2-C-methyl-d-erythritol-2,4-cyclodiphosphate synthase.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2019 Oct 15; Vol. 29 (20), pp. 126660. Date of Electronic Publication: 2019 Sep 03. - Publication Year :
- 2019
-
Abstract
- Enzymes in the methylerythritol phosphate pathway make attractive targets for antibacterial activity due to their importance in isoprenoid biosynthesis and the absence of the pathway in mammals. The fifth enzyme in the pathway, 2-C-methyl-d-erythritol-2,4-cyclodiphosphate synthase (IspF), contains a catalytically important zinc ion in the active site. A series of de novo designed compounds containing a zinc binding group was synthesized and evaluated for antibacterial activity and interaction with IspF from Burkholderia pseudomallei, the causative agent of Whitmore's disease. The series demonstrated antibacterial activity as well as protein stabilization in fluorescence-based thermal shift assays. Finally, the binding of one compound to Burkholderia pseudomallei IspF was evaluated through group epitope mapping by saturation transfer difference NMR.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Catalysis
Catalytic Domain
Crystallography, X-Ray
Erythritol biosynthesis
Humans
Kinetics
Molecular Structure
Protein Binding
Signal Transduction
Zinc chemistry
Anti-Bacterial Agents chemistry
Bacterial Proteins biosynthesis
Burkholderia pseudomallei enzymology
Erythritol analogs & derivatives
Phosphorus-Oxygen Lyases chemistry
Phosphorus-Oxygen Lyases metabolism
Pyrimidines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 29
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 31521478
- Full Text :
- https://doi.org/10.1016/j.bmcl.2019.126660