3f4b | pdb_00003f4b

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

spinqualitylabelsall models 3f4b, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3f4b is a 4 chain structure with sequence from Plasmodium berghei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.49Å Ligands: NAD, TCL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6TEI5_PLABE Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites.,Yu M, Kumar TR, Nkrumah LJ, Coppi A, Retzlaff S, Li CD, Kelly BJ, Moura PA, Lakshmanan V, Freundlich JS, Valderramos JC, Vilcheze C, Siedner M, Tsai JH, Falkard B, Sidhu AB, Purcell LA, Gratraud P, Kremer L, Waters AP, Schiehser G, Jacobus DP, Janse CJ, Ager A, Jacobs WR Jr, Sacchettini JC, Heussler V, Sinnis P, Fidock DA Cell Host Microbe. 2008 Dec 11;4(6):567-78. doi: 10.1016/j.chom.2008.11.001. PMID:19064257 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Enoyl-Acyl-Carrier Protein Reductase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA