7kpq

Crystal structure of CtdE in complex with FAD

spinqualitylabelsall models 7kpq, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7kpq is a 1 chain structure with sequence from Penicillium citrinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: FAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Prenylated indole alkaloids featuring spirooxindole rings possess a 3R or 3S carbon stereocenter, which determines the bioactivities of these compounds. Despite the stereoselective advantages of spirooxindole biosynthesis compared with those of organic synthesis, the biocatalytic mechanism for controlling the 3R or 3S-spirooxindole formation has been elusive. Here, we report an oxygenase/semipinacolase CtdE that specifies the 3S-spirooxindole construction in the biosynthesis of 21R-citrinadin A. High-resolution X-ray crystal structures of CtdE with the substrate and cofactor, together with site-directed mutagenesis and computational studies, illustrate the catalytic mechanisms for the possible beta-face epoxidation followed by a regioselective collapse of the epoxide intermediate, which triggers semipinacol rearrangement to form the 3S-spirooxindole. Comparing CtdE with PhqK, which catalyzes the formation of the 3R-spirooxindole, we reveal an evolutionary branch of CtdE in specific 3S spirocyclization. Our study provides deeper insights into the stereoselective catalytic machinery, which is important for the biocatalysis design to synthesize spirooxindole pharmaceuticals. Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins.,Liu Z, Zhao F, Zhao B, Yang J, Ferrara J, Sankaran B, Venkataram Prasad BV, Kundu BB, Phillips GN Jr, Gao Y, Hu L, Zhu T, Gao X Nat Commun. 2021 Jul 6;12(1):4158. doi: 10.1038/s41467-021-24421-0. PMID:34230497 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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