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Structural insights of isocitrate lyases from Magnaporthe oryzae
Structural highlights
FunctionACEA_MAGO7 Catalyzes the formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle, which operates as an anaplerotic route for replenishing the tricarboxylic acid cycle. Required for growth on ethanol or acetate, but dispensable when fermentable carbon sources are available. Acts also on 2-methylisocitrate (By similarity). plays an important role in plant pathogenicity.[UniProtKB:P28240][1] Publication Abstract from PubMedThe glyoxylate cycle bypasses a CO2-generating step in the tricarboxylic acid (TCA) cycle and efficiently assimilates C2 compounds into intermediates that can be used in later steps of the TCA cycle. It plays an essential role in pathogen survival during host infection such that the enzymes involved in this cycle have been suggested as potential drug targets against human pathogens. Isocitrate lyase (ICL) catalyzes the first-step reaction of the glyoxylate cycle, using isocitrate from the TCA cycle as the substrate to produce succinate and glyoxylate. In this study we report the crystal structure of Magnaporthe oryzae ICL in both the ligand-free form and as a complex with Mg(2+), glyoxylate, and glycerol, as well as the structure of the Fusarium graminearum ICL complexed with Mn(2+) and malonate. We also describe the ligand-induced conformational changes in the catalytic loop and C-terminal region, both of which are essential for catalysis. Using various mutant ICLs in an activity assay, we gained insight into the function of residues within the active site. These structural and functional analyses provide detailed information with regard to fungal ICLs. Crystal structure and functional analysis of isocitrate lyases from Magnaporthe oryzae and Fusarium graminearum.,Park Y, Cho Y, Lee YH, Lee YW, Rhee S J Struct Biol. 2016 Jun;194(3):395-403. doi: 10.1016/j.jsb.2016.03.019. Epub 2016, Mar 22. PMID:27016285[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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