3ICN

Trypanosoma cruzi farnesyl diphosphate synthase homodimer in complex with isopentenyl pyrophosphate and 3-Fluoro-1-(2-hydroxy-2,2-bis-phosphono-ethyl)-pyridinium

3ICN の概要

• エントリーDOI: 10.2210/pdb3icn/pdb
• 関連するPDBエントリー: 1YHK 1YHL 1YHM 3IBA 3ICK 3ICM 3ICZ 3ID0
• 分子名称: Farnesyl pyrophosphate synthase, 3-FLUORO-1-(2-HYDROXY-2,2-DIPHOSPHONOETHYL)PYRIDINIUM, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: farnesyl diphosphate synthase, fpps, bisphosphonate, zoledronate, risedronate, minodronate, chagas disease, isoprene biosynthesis, transferase
• 由来する生物種: Trypanosoma cruzi
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42038.57

構造登録者

Amzel, L.M.,Huang, C.H.,Gabelli, S.B.,Oldfield, E. (登録日: 2009-07-17, 公開日: 2010-02-09, 最終更新日: 2024-02-21)

主引用文献

Huang, C.H.,Gabelli, S.B.,Oldfield, E.,Amzel, L.M.
Binding of nitrogen-containing bisphosphonates (N-BPs) to the Trypanosoma cruzi farnesyl diphosphate synthase homodimer.
Proteins, 78:888-899, 2010

PubMed Abstract: Bisphosphonates (BPs) are a class of compounds that have been used extensively in the treatment of osteoporosis and malignancy-related hypercalcemia. Some of these compounds act through inhibition of farnesyl diphosphate synthase (FPPS), a key enzyme in the synthesis of isoprenoids. Recently, nitrogen-containing bisphosphonates (N-BPs) used in bone resorption therapy have been shown to be active against Trypanosoma cruzi, the parasite that causes American trypanosomiasis (Chagas disease), suggesting that they may be used as anti-trypanosomal agents. The crystal structures of TcFPPS in complex with substrate (isopentenyl diphosphate, IPP) and five N-BP inhibitors show that the C-1 hydroxyl and the nitrogen-containing groups of the inhibitors alter the binding of IPP and the conformation of two TcFPPS residues, Tyr94 and Gln167. Isothermal titration calorimetry experiments suggest that binding of the first N-BPs to the homodimeric TcFPPS changes the binding properties of the second site. This mechanism of binding of N-BPs to TcFPPS is different to that reported for the binding of the same compounds to human FPPS. Proteins 2010. (c) 2009 Wiley-Liss, Inc.

PubMed: 19876942
DOI: 10.1002/prot.22614

実験手法

X-RAY DIFFRACTION (2.4 Å)