3FBA
Crystal structure of 2C-methyl-D-erythritol 2,4-clycodiphosphate synthase complexed with ligand
Summary for 3FBA
| Entry DOI | 10.2210/pdb3fba/pdb |
| Descriptor | 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, ZINC ION, [(2S,3S,4R,5S)-5-(4-amino-2-oxo-pyrimidin-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] dihydrogen phosphate, ... (6 entities in total) |
| Functional Keywords | mecdp-synthase, lyase, isoprene biosynthesis, magnesium, manganese, metal-binding |
| Biological source | Escherichia coli |
| Total number of polymer chains | 1 |
| Total formula weight | 18371.18 |
| Authors | Hunter, W.N.,Ramsden, N.L. (deposition date: 2008-11-19, release date: 2009-08-25, Last modification date: 2023-11-01) |
| Primary citation | Ramsden, N.L.,Buetow, L.,Dawson, A.,Kemp, L.A.,Ulaganathan, V.,Brenk, R.,Klebe, G.,Hunter, W.N. A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy J.Med.Chem., 52:2531-2542, 2009 Cited by PubMed Abstract: The nonmevalonate route to isoprenoid biosynthesis is essential in Gram-negative bacteria and apicomplexan parasites. The enzymes of this pathway are absent from mammals, contributing to their appeal as chemotherapeutic targets. One enzyme, 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase (IspF), has been validated as a target by genetic approaches in bacteria. Virtual screening against Escherichia coli IspF (EcIspF) was performed by combining a hierarchical filtering methodology with molecular docking. Docked compounds were inspected and 10 selected for experimental validation. A surface plasmon resonance assay was developed and two weak ligands identified. Crystal structures of EcIspF complexes were determined to support rational ligand development. Cytosine analogues and Zn(2+)-binding moieties were characterized. One of the putative Zn(2+)-binding compounds gave the lowest measured K(D) to date (1.92 +/- 0.18 muM). These data provide a framework for the development of IspF inhibitors to generate lead compounds of therapeutic potential against microbial pathogens. PubMed: 19320487DOI: 10.1021/jm801475n PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.1 Å) |
Structure validation
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