| Structural highlights
4nai is a 1 chain structure with sequence from Arath. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | CD, K |
| Related: | 1w77, 2yc5, 1ini, 4nak, 4nal, 4nan |
| Gene: | At2g02500, ISPD, MCT, MECT, MEPCT, T8K22.20 (ARATH) |
| Activity: | 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase, with EC number 2.7.7.60 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[ISPD_ARATH] Enzyme of the plastid non-mevalonate pathway for isoprenoid biosynthesis that catalyzes the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from CTP and 2-C-methyl-D-erythritol 4-phosphate (MEP). Is essential for chloroplast development and required for pigments and gibberellins biosynthesis.[1] [2] [3]
Publication Abstract from PubMed
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.
Pseudilins: Halogenated, Allosteric Inhibitors of the Non-Mevalonate Pathway Enzyme IspD.,Kunfermann A, Witschel M, Illarionov B, Martin R, Rottmann M, Hoffken HW, Seet M, Eisenreich W, Knolker HJ, Fischer M, Bacher A, Groll M, Diederich F Angew Chem Int Ed Engl. 2014 Jan 20. doi: 10.1002/anie.201309557. PMID:24446431[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rohdich F, Wungsintaweekul J, Eisenreich W, Richter G, Schuhr CA, Hecht S, Zenk MH, Bacher A. Biosynthesis of terpenoids: 4-diphosphocytidyl-2C-methyl-D-erythritol synthase of Arabidopsis thaliana. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6451-6. PMID:10841550
- ↑ Okada K, Kawaide H, Kuzuyama T, Seto H, Curtis IS, Kamiya Y. Antisense and chemical suppression of the nonmevalonate pathway affects ent-kaurene biosynthesis in Arabidopsis. Planta. 2002 Jun;215(2):339-44. Epub 2002 Apr 12. PMID:12029484 doi:https://dx.doi.org/10.1007/s00425-002-0762-0
- ↑ Hsieh MH, Chang CY, Hsu SJ, Chen JJ. Chloroplast localization of methylerythritol 4-phosphate pathway enzymes and regulation of mitochondrial genes in ispD and ispE albino mutants in Arabidopsis. Plant Mol Biol. 2008 Apr;66(6):663-73. doi: 10.1007/s11103-008-9297-5. Epub 2008 , Jan 31. PMID:18236010 doi:https://dx.doi.org/10.1007/s11103-008-9297-5
- ↑ Kunfermann A, Witschel M, Illarionov B, Martin R, Rottmann M, Hoffken HW, Seet M, Eisenreich W, Knolker HJ, Fischer M, Bacher A, Groll M, Diederich F. Pseudilins: Halogenated, Allosteric Inhibitors of the Non-Mevalonate Pathway Enzyme IspD. Angew Chem Int Ed Engl. 2014 Jan 20. doi: 10.1002/anie.201309557. PMID:24446431 doi:https://dx.doi.org/10.1002/anie.201309557
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