9zo1

Crystal structure of deoxypodophyllotoxin synthase (DPS) complexed with vanadyl(IV)-oxo, succinate and (-)-hydroxy-yatein

spinqualitylabelsall models 9zo1, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9zo1 is a 2 chain structure with sequence from Sinopodophyllum hexandrum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: A1C3S, CL, EDO, GOL, SIN, VVO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 2ODD_SINHE Publication Abstract from PubMed The lignan (-)-podophyllotoxin possesses significant antiviral and anticancer activities and thus serves as a precursor to several natural products with therapeutic properties. Biosynthesis of podophyllotoxin involves cyclization of (-)-yatein to yield deoxypodophyllotoxin catalyzed by the iron- and alpha-ketoglutarate-dependent (Fe/alpha-KG) oxidase deoxypodophyllotoxin synthase (DPS), which completes the tetracyclic core of podophyllotoxin. Herein, (+)-hydroxy-yatein is also shown to be a substrate for DPS, directly affording (-)-podophyllotoxin as the enzymatic product. Moreover, derivatives of (+)-hydroxy-yatein are also found to be substrates providing synthetic precursors to medicines such as etoposide. Mechanistic analyses utilizing isotopologs and diastereomers of the m-dimethoxy analogue of (+)-hydroxy-yatein indicate antarafacial C-C bond formation during the cyclization reaction and remain consistent with cation-mediated cyclization. A crystallographic study of DPS bound with vanadium(IV) oxide, succinate, and (-)-hydroxy-yatein suggests a subtle interplay of steric interactions between the substrate and the active site that can alter the course of the DPS-catalyzed reaction and thus cyclization versus hydroxylation. Finally, an efficient chemoenzymatic approach to (-)-podophyllotoxin is described that relies only on freeze-dried whole cells after DPS overexpression. Biocatalytic Applications and Mechanistic Insights of Deoxypodophyllotoxin Synthase.,Michael C, Zheng YC, Ruszczycky MW, Chen NQ, Lin CH, Lin WY, Chang WC J Am Chem Soc. 2026 Apr 22;148(15):16394-16403. doi: 10.1021/jacs.6c03159. Epub , 2026 Apr 7. PMID:41946671 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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