4NAL

Arabidopsis thaliana IspD in complex with tribromodichloro-pseudilin

4NAL の概要

• エントリーDOI: 10.2210/pdb4nal/pdb
• 関連するPDBエントリー: 1INI 1W77 2YC5 4NAI 4NAK 4NAN
• 分子名称: 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)
• 機能のキーワード: herbicide, anti-infectives, pseudilin, natural product, drug discovery, allosteric inhibition, rossmann fold, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Arabidopsis thaliana (mouse-ear cress, thale-cress)
• 細胞内の位置: Plastid, chloroplast stroma (Probable): P69834
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26884.95

構造登録者

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. (登録日: 2013-10-22, 公開日: 2014-01-29, 最終更新日: 2023-09-20)

主引用文献

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

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: 24446431
DOI: 10.1002/anie.201309557

実験手法

X-RAY DIFFRACTION (1.8 Å)