3F4B

Crystal structure of Plasmodium berghei Enoyl-acyl-carrier-protein reductase with TRICLOSAN

3F4B の概要

• エントリーDOI: 10.2210/pdb3f4b/pdb
• 関連するPDBエントリー: 1NHG
• 分子名称: Enoyl-acyl carrier protein reductase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, TRICLOSAN, ... (4 entities in total)
• 機能のキーワード: pbenr, pbfabi, triclosan, oxidoreductase
• 由来する生物種: Plasmodium berghei
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 147529.21

構造登録者

Sacchettini, J.C.,Tsai, H.-C. (登録日: 2008-10-31, 公開日: 2010-03-02, 最終更新日: 2023-09-06)

主引用文献

Yu, M.,Kumar, T.R.,Nkrumah, L.J.,Coppi, A.,Retzlaff, S.,Li, C.D.,Kelly, B.J.,Moura, P.A.,Lakshmanan, V.,Freundlich, J.S.,Valderramos, J.C.,Vilcheze, C.,Siedner, M.,Tsai, J.H.,Falkard, B.,Sidhu, A.B.,Purcell, L.A.,Gratraud, P.,Kremer, L.,Waters, A.P.,Schiehser, G.,Jacobus, D.P.,Janse, C.J.,Ager, A.,Jacobs, W.R.,Sacchettini, J.C.,Heussler, V.,Sinnis, P.,Fidock, D.A.
The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites.
Cell Host Microbe, 4:567-578, 2008

PubMed Abstract: The fatty acid synthesis type II pathway has received considerable interest as a candidate therapeutic target in Plasmodium falciparum asexual blood-stage infections. This apicoplast-resident pathway, distinct from the mammalian type I process, includes FabI. Here, we report synthetic chemistry and transfection studies concluding that Plasmodium FabI is not the target of the antimalarial activity of triclosan, an inhibitor of bacterial FabI. Disruption of fabI in P. falciparum or the rodent parasite P. berghei does not impede blood-stage growth. In contrast, mosquito-derived, FabI-deficient P. berghei sporozoites are markedly less infective for mice and typically fail to complete liver-stage development in vitro. This defect is characterized by an inability to form intrahepatic merosomes that normally initiate blood-stage infections. These data illuminate key differences between liver- and blood-stage parasites in their requirements for host versus de novo synthesized fatty acids, and create new prospects for stage-specific antimalarial interventions.

PubMed: 19064257
DOI: 10.1016/j.chom.2008.11.001

実験手法

X-RAY DIFFRACTION (2.49 Å)