8su2

F96H epi-Isozizaene Synthase: complex with 3 Mg2+ and risedronate

spinqualitylabelsall models 8su2, resolution 1.33Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8su2 is a 1 chain structure with sequence from Streptomyces coelicolor A3(2). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.33Å Ligands: GOL, MG, RIS, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CYC1_STRCO Catalyzes the cyclization of farnesyl diphosphate (FPP) to the sesquiterpene epi-isozizaene. Publication Abstract from PubMed The class I sesquiterpene cyclase epi-isozizaene synthase from Streptomyces coelicolor (EIZS) catalyzes the transformation of linear farnesyl diphosphate (FPP) into the tricyclic hydrocarbon epi-isozizaene in the biosynthesis of albaflavenone antibiotics. The active site cavity of EIZS is largely framed by four aromatic residues - F95, F96, F198, and W203 - that form a product-shaped contour, serving as a template to chaperone conformations of the flexible substrate and multiple carbocation intermediates leading to epi-isozizaene. Remolding the active site contour by mutagenesis can redirect the cyclization cascade away from epi-isozizaene biosynthesis to generate alternative sesquiterpene products. Here, we present the biochemical and structural characterization of four EIZS mutants in which aromatic residues have been substituted with polar residues (F95S, F96H, F198S, and F198T) to generate alternative cyclization products. Most notably, F95S EIZS generates a mixture of monocyclic sesquiterpene precursors of bisabolane, a D2 diesel fuel substitute. X-ray crystal structures of the characterized mutants reveal subtle changes in the active site contour showing how each aromatic residue influences the chemistry of a different carbocation intermediate in the cyclization cascade. We advance that EIZS may serve as a robust platform for the development of designer cyclases for the generation of high-value sesquiterpene products ranging from pharmaceuticals to biofuels in synthetic biology approaches. Reprogramming the Cyclization Cascade of epi-Isozizaene Synthase to Generate Alternative Terpene Products.,Eaton SA, Christianson DW Biochemistry. 2023 Jul 14. doi: 10.1021/acs.biochem.3c00247. PMID:37449555 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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