1ONO
IspC Mn2+ complex
Summary for 1ONO
| Entry DOI | 10.2210/pdb1ono/pdb |
| Related | 1ONN 1ONP |
| Descriptor | 1-deoxy-D-xylulose 5-phosphate reductoisomerase, MANGANESE (II) ION (3 entities in total) |
| Functional Keywords | isoprenoid biosynthesis, mevalonate-independent pathway, ispc, oxidoreductase |
| Biological source | Escherichia coli |
| Total number of polymer chains | 2 |
| Total formula weight | 86973.63 |
| Authors | Steinbacher, S.,Kaiser, J.,Eisenreich, W.,Huber, R.,Bacher, A.,Rohdich, F. (deposition date: 2003-02-28, release date: 2003-03-18, Last modification date: 2023-10-25) |
| Primary citation | Steinbacher, S.,Kaiser, J.,Eisenreich, W.,Huber, R.,Bacher, A.,Rohdich, F. Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-D-erythritol 4-phosphate synthase (IspC). Implications for the catalytic mechanism and anti-malaria drug development. J.BIOL.CHEM., 278:18401-18407, 2003 Cited by PubMed Abstract: 2-C-Methyl-d-erythritol 4-phosphate synthase (IspC) is the first enzyme committed to isoprenoid biosynthesis in the methylerythritol phosphate pathway, which represents an alternative route to the classical mevalonate pathway. As it is present in many pathogens and plants, but not in man, this pathway has attracted considerable interest as a target for novel antibiotics and herbicides. Fosmidomycin represents a specific high-affinity inhibitor of IspC. Very recently, its anti-malaria activity in man has been demonstrated in clinical trials. Here, we present the crystal structure of Escherichia coli IspC in complex with manganese and fosmidomycin at 2.5 A resolution. The (N-formyl-N-hydroxy)amino group provides two oxygen ligands to manganese that is present in a distorted octahedral coordination, whereas the phosphonate group is anchored in a specific pocket by numerous hydrogen bonds. Both sites are connected by a spacer of three methylene groups. The substrate molecule, 1-d-deoxyxylulose 5-phosphate, can be superimposed onto fosmidomycin, explaining the stereochemical course of the reaction. PubMed: 12621040DOI: 10.1074/jbc.M300993200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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