9ZO1
Crystal structure of deoxypodophyllotoxin synthase (DPS) complexed with vanadyl(IV)-oxo, succinate and (-)-hydroxy-yatein
This is a non-PDB format compatible entry.
Summary for 9ZO1
| Entry DOI | 10.2210/pdb9zo1/pdb |
| Descriptor | Deoxypodophyllotoxin synthase, oxovanadium(2+), (3S,4S)-4-[(S)-(2H-1,3-benzodioxol-5-yl)(hydroxy)methyl]-3-[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one, ... (8 entities in total) |
| Functional Keywords | oxygenase, fe/2og, oxidoreductase |
| Biological source | Sinopodophyllum hexandrum |
| Total number of polymer chains | 2 |
| Total formula weight | 73892.37 |
| Authors | |
| Primary citation | Michael, C.,Zheng, Y.C.,Ruszczycky, M.W.,Chen, N.Q.,Lin, C.H.,Lin, W.Y.,Chang, W.C. Biocatalytic Applications and Mechanistic Insights of Deoxypodophyllotoxin Synthase. J.Am.Chem.Soc., 148:16394-16403, 2026 Cited by PubMed Abstract: 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 α-ketoglutarate-dependent (Fe/α-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 -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. PubMed: 41946671DOI: 10.1021/jacs.6c03159 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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