5AEL

T. Brucei Farnesyl Diphosphate Synthase Complexed with Bisphosphonate BPH-597

5AEL の概要

• エントリーDOI: 10.2210/pdb5ael/pdb
• 分子名称: FARNESYL PYROPHOSPHATE SYNTHASE, {2-[3-(hex-1-yn-1-yl)pyridinium-1-yl]ethane-1,1-diyl}bis(phosphonate), MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: TRYPANOSOMA BRUCEI
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84864.36

構造登録者

Yang, G.,Oldfield, E.,No, J.H. (登録日: 2014-12-26, 公開日: 2015-10-28, 最終更新日: 2024-01-10)

主引用文献

Yang, G.,Zhu, W.,Kim, K.,Byun, S.Y.,Choi, G.,Wang, K.,Cha, J.S.,Cho, H.,Oldfield, E.,No, J.H.
Inhibition of Trypanosoma Brucei Cell Growth by Lipophilic Bisphosphonates: An in Vitro and in Vivo Investigation.
Antimicrob.Agents Chemother., 59:7530-, 2015

PubMed Abstract: We report the results of a screen of a library of 925 potential prenyl synthase inhibitors against Trypanosoma brucei farnesyl diphosphate synthase (TbFPPS) and against T. brucei, the causative agent of human African trypanosomiasis. The most potent compounds were lipophilic analogs of the bone resorption drug zoledronate, some of which had submicromolar to low micromolar activity against bloodstream form T. brucei and selectivity indices of up to ∼ 300. We evaluated the effects of two such inhibitors on survival and parasitemia in a T. brucei mouse model of infection and found that survival increased by up to 16 days. We also investigated the binding of three lipophilic bisphosphonates to an expressed TbFPPS using crystallography and investigated the thermodynamics of binding using isothermal titration calorimetry.

PubMed: 26392508
DOI: 10.1128/AAC.01873-15

実験手法

X-RAY DIFFRACTION (2.6 Å)