4KP7
Structure of Plasmodium IspC in complex with a beta-thia-isostere derivative of Fosmidomycin
Summary for 4KP7
Entry DOI | 10.2210/pdb4kp7/pdb |
Related | 3AU8 3AU9 |
Descriptor | 1-deoxy-D-xylulose 5-phosphate reductoisomerase, apicoplast, MANGANESE (III) ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total) |
Functional Keywords | dxp pathway, drug optimization, non-covalent inhibition, malaria, tuberculosis, rossmann fold, reductoisomerase, nadph binding, apicoplast, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor |
Biological source | Plasmodium falciparum |
Cellular location | Plastid, apicoplast: O96693 |
Total number of polymer chains | 2 |
Total formula weight | 98739.81 |
Authors | Kunfermann, A.,Bacher, A.,Groll, M. (deposition date: 2013-05-13, release date: 2013-10-02, Last modification date: 2023-09-20) |
Primary citation | Kunfermann, A.,Lienau, C.,Illarionov, B.,Held, J.,Grawert, T.,Behrendt, C.T.,Werner, P.,Hahn, S.,Eisenreich, W.,Riederer, U.,Mordmuller, B.,Bacher, A.,Fischer, M.,Groll, M.,Kurz, T. IspC as Target for Antiinfective Drug Discovery: Synthesis, Enantiomeric Separation, and Structural Biology of Fosmidomycin Thia Isosters. J.Med.Chem., 56:8151-8162, 2013 Cited by PubMed Abstract: The emergence and spread of multidrug-resistant pathogens are widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the synthesis and properties of "reverse" thia analogs of fosmidomycin, which inhibit the first committed enzyme of a metabolic pathway that is essential for the causative agents of tuberculosis and malaria but is absent in the human host. Notably, IspC displays a high level of enantioselectivity for an α-substituted fosmidomycin derivative. PubMed: 24032981DOI: 10.1021/jm4012559 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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