4NAL
Arabidopsis thaliana IspD in complex with tribromodichloro-pseudilin
Summary for 4NAL
| Entry DOI | 10.2210/pdb4nal/pdb |
| Related | 1INI 1W77 2YC5 4NAI 4NAK 4NAN |
| Descriptor | 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase, chloroplastic, 2,4-DICHLORO-6-(3,4,5-TRIBROMO-1H-PYRROL-2-YL)PHENOL, 2,3-DIHYDROXY-1,4-DITHIOBUTANE, ... (6 entities in total) |
| Functional Keywords | herbicide, anti-infectives, pseudilin, natural product, drug discovery, allosteric inhibition, rossmann fold, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Arabidopsis thaliana (mouse-ear cress, thale-cress) |
| Cellular location | Plastid, chloroplast stroma (Probable): P69834 |
| Total number of polymer chains | 1 |
| Total formula weight | 26884.95 |
| Authors | Kunfermann, A.,Witschel, M.,Illarionov, B.,Martin, R.,Rottmann, M.,Hoffken, H.W.,Seet, M.,Eisenreich, W.,Knolker, H.-J.,Fischer, M.,Bacher, A.,Groll, M.,Diederich, F. (deposition date: 2013-10-22, release date: 2014-01-29, Last modification date: 2023-09-20) |
| Primary citation | Kunfermann, A.,Witschel, M.,Illarionov, B.,Martin, R.,Rottmann, M.,Hoffken, H.W.,Seet, M.,Eisenreich, W.,Knolker, H.J.,Fischer, M.,Bacher, A.,Groll, M.,Diederich, F. Pseudilins: Halogenated, Allosteric Inhibitors of the Non-Mevalonate Pathway Enzyme IspD. Angew.Chem.Int.Ed.Engl., 53:2235-2239, 2014 Cited by PubMed Abstract: The enzymes of the non-mevalonate pathway for isoprenoid biosynthesis have been identified as attractive targets with novel modes of action for the development of herbicides for crop protection and agents against infectious diseases. This pathway is present in many pathogenic organisms and plants, but absent in mammals. By using high-throughput screening, we identified highly halogenated marine natural products, the pseudilins, to be inhibitors of the third enzyme, IspD, in the pathway. Their activity against the IspD enzymes from Arabidopsis thaliana and Plasmodium vivax was determined in photometric and NMR-based assays. Cocrystal structures revealed that pseudilins bind to an allosteric pocket by using both divalent metal ion coordination and halogen bonding. The allosteric mode of action for preventing cosubstrate (CTP) binding at the active site was elucidated. Pseudilins show herbicidal activity in plant assays and antiplasmodial activity in cell-based assays. PubMed: 24446431DOI: 10.1002/anie.201309557 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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