Type I and type II fatty acid biosynthesis inEimeria tenella: enoyl reductase activity and structure
- 1 March 2007
- journal article
- research article
- Published by Cambridge University Press (CUP) in Parasitology
- Vol. 134 (14), 1949-1962
- https://doi.org/10.1017/s0031182007003319
Abstract
Apicomplexan parasites of the genus Eimeria are the major causative agent of avian coccidiosis, leading to high economic losses in the poultry industry. Recent results show that Eimeria tenella harbours an apicoplast organelle, and that a key biosynthetic enzyme, enoyl reductase, is located in this organelle. In related parasites, enoyl reductase is one component of a type II fatty acid synthase (FAS) and has proven to be an attractive target for antimicrobial compounds. We cloned and expressed the mature form of E. tenella enoyl reductase (EtENR) for biochemical and structural studies. Recombinant EtENR exhibits NADH-dependent enoyl reductase activity and is inhibited by triclosan with an IC50 value of 60 nm. The crystal structure of EtENR reveals overall similarity with other ENR enzymes; however, the active site of EtENR is unoccupied, a state rarely observed in other ENR structures. Furthermore, the position of the central beta-sheet appears to block NADH binding and would require significant movement to allow NADH binding, a feature not previously seen in the ENR family. We analysed the E. tenella genomic database for orthologues of well-characterized bacterial and apicomplexan FAS enzymes and identified 6 additional genes, suggesting that E. tenella contains a type II FAS capable of synthesizing saturated, but not unsaturated, fatty acids. Interestingly, we also identified sequences that appear to encode multifunctional type I FAS enzymes, a feature also observed in Toxoplasma gondii, highlighting the similarity between these apicomplexan parasites.Keywords
This publication has 68 references indexed in Scilit:
- Studies ofToxoplasma gondiiandPlasmodium falciparumenoyl acyl carrier protein reductase and implications for the development of antiparasitic agentsActa Crystallographica Section D-Structural Biology, 2007
- Enzymes of type II fatty acid synthesis and apicoplast differentiation and division in Eimeria tenellaInternational Journal for Parasitology, 2007
- Scavenging of the cofactor lipoate is essential for the survival of the malaria parasite Plasmodium falciparumMolecular Microbiology, 2007
- Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival inToxoplasma gondiiProceedings of the National Academy of Sciences of the United States of America, 2006
- Toxoplasma gondii scavenges host-derived lipoic acid despite its de novo synthesis in the apicoplastThe EMBO Journal, 2006
- Expression, purification and preliminary crystallographic analysis of theToxoplasma gondiienoyl reductaseActa Crystallographica Section F Structural Biology and Crystallization Communications, 2006
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004
- XtalView/Xfit—A Versatile Program for Manipulating Atomic Coordinates and Electron DensityJournal of Structural Biology, 1999
- [20] Processing of X-ray diffraction data collected in oscillation modeMethods in Enzymology, 1997
- The CCP4 suite: programs for protein crystallographyActa Crystallographica Section D-Biological Crystallography, 1994