1ONP

IspC complex with Mn2+ and fosmidomycin

1ONP の概要

• エントリーDOI: 10.2210/pdb1onp/pdb
• 関連するPDBエントリー: 1ONN 1ONO
• 分子名称: 1-deoxy-D-xylulose 5-phosphate reductoisomerase, MANGANESE (II) ION, 3-[FORMYL(HYDROXY)AMINO]PROPYLPHOSPHONIC ACID, ... (4 entities in total)
• 機能のキーワード: isoprenoid biosynthesis, mevalonate-independent pathway, ispc, oxidoreductase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 87339.83

構造登録者

Steinbacher, S.,Kaiser, J.,Eisenreich, W.,Huber, R.,Bacher, A.,Rohdich, F. (登録日: 2003-02-28, 公開日: 2003-03-18, 最終更新日: 2023-10-25)

主引用文献

Steinbacher, S.,Kaiser, J.,Eisenreich, W.,Huber, R.,Bacher, A.,Rohdich, F.
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.
J.BIOL.CHEM., 278:18401-18407, 2003

PubMed Abstract: 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.

PubMed: 12621040
DOI: 10.1074/jbc.M300993200

実験手法

X-RAY DIFFRACTION (2.5 Å)