4MUX

IspH in complex with pyridin-3-ylmethyl diphosphate

4MUX の概要

• エントリーDOI: 10.2210/pdb4mux/pdb
• 関連するPDBエントリー: 3DNF 3F7T 3KE8 4MUX 4MUY 4MV0 4MV5
• 分子名称: 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, IRON/SULFUR CLUSTER, pyridin-3-ylmethyl trihydrogen diphosphate, ... (4 entities in total)
• 機能のキーワード: iron-sulfur protein, reductase, pyridin-3-ylmethyl diphosphate, cytosol, 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: 73457.33

構造登録者

Span, I.,Eisenreich, W.,Bacher, A.,Oldfield, E.,Groll, M. (登録日: 2013-09-23, 公開日: 2014-06-18, 最終更新日: 2024-02-28)

主引用文献

Span, I.,Wang, K.,Eisenreich, W.,Bacher, A.,Zhang, Y.,Oldfield, E.,Groll, M.
Insights into the Binding of Pyridines to the Iron-Sulfur Enzyme IspH.
J.Am.Chem.Soc., 136:7926-7932, 2014

PubMed Abstract: (E)-1-Hydroxy-2-methylbut-2-enyl 4-diphosphate reductase (IspH) is a [Fe4S4] cluster-containing enzyme involved in isoprenoid biosynthesis in many bacteria as well as in malaria parasites and is an important drug target. Several inhibitors including amino and thiol substrate analogues, as well as acetylene and pyridine diphosphates, have been reported. Here, we investigate the mode of binding of four pyridine diphosphates to Escherichia coli IspH by using X-ray crystallography. In three cases, one of the iron atoms in the cluster is absent, but in the structure with (pyridin-3-yl)methyl diphosphate, the most potent pyridine-analogue inhibitor reported previously, the fourth iron of the [Fe4S4] cluster is present and interacts with the pyridine ring of the ligand. Based on the results of quantum chemical calculations together with the crystallographic results we propose a side-on η(2) coordination of the nitrogen and the carbon in the 2-position of the pyridine ring to the unique fourth iron in the cluster, which is in the reduced state. The X-ray structure enables excellent predictions using density functional theory of the (14)N hyperfine coupling and quadrupole coupling constants reported previously using HYSCORE spectroscopy, as well as providing a further example of the ability of such [Fe4S4]-containing proteins to form organometallic complexes.

PubMed: 24813236
DOI: 10.1021/ja501127j

実験手法

X-RAY DIFFRACTION (1.7 Å)