2e4o

X-ray Crystal Structure of Aristolochene Synthase from Aspergillus terreus and the Evolution of Templates for the Cyclization of Farnesyl Diphosphate

spinqualitylabelsall models 2e4o, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2e4o is a 4 chain structure with sequence from Aspte. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BME, CL, MES Related: 1di1, 2oa6 Gene: Ari1 (ASPTE) Activity: Aristolochene synthase, with EC number 4.2.3.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [ARIS_ASPTE] Catalyzes the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic sesquiterpene aristolochene. Produces germacrene A as an enzyme-bound intermediate that is not released by the enzyme, but is further cyclized to produce aristolochene. Aristolochene is the likely parent compound for a number of sesquiterpenoid toxins produced by filamentous fungi. 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 Aristolochene synthase from Aspergillus terreus catalyzes the cyclization of the universal sesquiterpene precursor, farnesyl diphosphate, to form the bicyclic hydrocarbon aristolochene. The 2.2 A resolution X-ray crystal structure of aristolochene synthase reveals a tetrameric quaternary structure in which each subunit adopts the alpha-helical class I terpene synthase fold with the active site in the "open", solvent-exposed conformation. Intriguingly, the 2.15 A resolution crystal structure of the complex with Mg2+3-pyrophosphate reveals ligand binding only to tetramer subunit D, which is stabilized in the "closed" conformation required for catalysis. Tetramer assembly may hinder conformational changes required for the transition from the inactive open conformation to the active closed conformation, thereby accounting for the attenuation of catalytic activity with an increase in enzyme concentration. In both conformations, but especially in the closed conformation, the active site contour is highly complementary in shape to that of aristolochene, and a catalytic function is proposed for the pyrophosphate anion based on its orientation with regard to the presumed binding mode of aristolochene. A similar active site contour is conserved in aristolochene synthase from Penicillium roqueforti despite the substantial divergent evolution of these two enzymes, while strikingly different active site contours are found in the sesquiterpene cyclases 5-epi-aristolochene synthase and trichodiene synthase. Thus, the terpenoid cyclase active site plays a critical role as a template in binding the flexible polyisoprenoid substrate in the proper conformation for catalysis. Across the greater family of terpenoid cyclases, this template is highly evolvable within a conserved alpha-helical fold for the synthesis of terpene natural products of diverse structure and stereochemistry. X-ray crystal structure of aristolochene synthase from Aspergillus terreus and evolution of templates for the cyclization of farnesyl diphosphate.,Shishova EY, Di Costanzo L, Cane DE, Christianson DW Biochemistry. 2007 Feb 20;46(7):1941-51. Epub 2007 Jan 30. PMID:17261032 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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