3F4B
Crystal structure of Plasmodium berghei Enoyl-acyl-carrier-protein reductase with TRICLOSAN
Summary for 3F4B
| Entry DOI | 10.2210/pdb3f4b/pdb |
| Related | 1NHG |
| Descriptor | Enoyl-acyl carrier protein reductase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, TRICLOSAN, ... (4 entities in total) |
| Functional Keywords | pbenr, pbfabi, triclosan, oxidoreductase |
| Biological source | Plasmodium berghei |
| Total number of polymer chains | 4 |
| Total formula weight | 147529.21 |
| Authors | Sacchettini, J.C.,Tsai, H.-C. (deposition date: 2008-10-31, release date: 2010-03-02, Last modification date: 2023-09-06) |
| Primary citation | 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 Cited by 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: 19064257DOI: 10.1016/j.chom.2008.11.001 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.49 Å) |
Structure validation
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