9zo1: Difference between revisions

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'''Unreleased structure'''


The entry 9zo1 is ON HOLD  until Paper Publication
==Crystal structure of deoxypodophyllotoxin synthase (DPS) complexed with vanadyl(IV)-oxo, succinate and (-)-hydroxy-yatein==
<StructureSection load='9zo1' size='340' side='right'caption='[[9zo1]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9zo1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sinopodophyllum_hexandrum Sinopodophyllum hexandrum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ZO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ZO1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1C3S:(3S,4S)-4-[(S)-(2H-1,3-benzodioxol-5-yl)(hydroxy)methyl]-3-[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one'>A1C3S</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=VVO:oxidanylidenevanadium(2+)'>VVO</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9zo1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9zo1 OCA], [https://pdbe.org/9zo1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9zo1 RCSB], [https://www.ebi.ac.uk/pdbsum/9zo1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9zo1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/2ODD_SINHE 2ODD_SINHE]
<div style="background-color:#fffaf0;">
== 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.


Authors: Michael, C., Zheng, Y.-C., Chang, W.-c.
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<ref>PMID:41946671</ref>


Description: Crystal structure of deoxypodophyllotoxin synthase (DPS) complexed with vanadyl(IV)-oxo, succinate and (-)-hydroxy-yatein
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Zheng, Y.-C]]
<div class="pdbe-citations 9zo1" style="background-color:#fffaf0;"></div>
[[Category: Michael, C]]
== References ==
[[Category: Chang, W.-C]]
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sinopodophyllum hexandrum]]
[[Category: Chang W-c]]
[[Category: Michael C]]
[[Category: Zheng Y-C]]
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