1ono
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IspC Mn2+ complex
OverviewOverview
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.
About this StructureAbout this Structure
1ONO is a Single protein structure of sequence from Escherichia coli with MN as ligand. Active as 1-deoxy-D-xylulose-5-phosphate reductoisomerase, with EC number 1.1.1.267 Full crystallographic information is available from OCA.
ReferenceReference
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., Steinbacher S, Kaiser J, Eisenreich W, Huber R, Bacher A, Rohdich F, J Biol Chem. 2003 May 16;278(20):18401-7. Epub 2003 Mar 5. PMID:12621040
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