1T1S

Crystal Structure of the Reductoisomerase Complexed with a Bisphosphonate

1T1S の概要

• エントリーDOI: 10.2210/pdb1t1s/pdb
• 関連するPDBエントリー: 1JVS 1T1R
• 分子名称: 1-deoxy-D-xylulose 5-phosphate reductoisomerase, SULFATE ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: three domains, 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: 87536.99

構造登録者

Yajima, S.,Hara, K.,Sanders, J.M.,Yin, F.,Ohsawa, K.,Wiesner, J.,Jomaa, H.,Oldfield, E. (登録日: 2004-04-17, 公開日: 2004-09-14, 最終更新日: 2024-03-13)

主引用文献

Yajima, S.,Hara, K.,Sanders, J.M.,Yin, F.,Ohsawa, K.,Wiesner, J.,Jomaa, H.,Oldfield, E.
Crystallographic Structures of Two Bisphosphonate:1-Deoxyxylulose-5-Phosphate Reductoisomerase Complexes
J.Am.Chem.Soc., 126:10824-10825, 2004

PubMed Abstract: We have obtained the single-crystal X-ray crystallographic structures of the bisphosphonates [(1-isoquinolinylamino)methylene]-1,1-bisphosphonate and [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate, bound to the enzyme 1-deoxyxylulose-5-phosphate reductoisomerase (DXR, EC 1.1.1.267, also known as 2-C-methyl-d-erythritol-4-phosphate synthase), an important target for the development of antimalarial drugs. Our results indicate that both bisphosphonates bind into the fosmidomycin binding site. The aromatic groups are in a shallow hydrophobic pocket, and the phosphonate groups are involved in electrostatic interactions with Mg2+ or a cluster of carboxylic acid groups and lysine while the fosmidomycin phosphonate-binding site is occupied by a sulfate ion (as also observed in the DXR/NADP+ structure). The availability of these two new crystal structures opens up the possibility of the further development of bisphosphonates and related systems as DXR inhibitors and, potentially, as antiinfective agents.

PubMed: 15339150
DOI: 10.1021/ja040126m

実験手法

X-RAY DIFFRACTION (2.4 Å)