7e38
From Proteopedia
(Difference between revisions)
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<StructureSection load='7e38' size='340' side='right'caption='[[7e38]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='7e38' size='340' side='right'caption='[[7e38]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'> | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E38 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E38 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]] 2.05Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=YTC:(3~{S},4~{S})-4-(1,3-benzodioxol-5-ylmethyl)-3-[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one'>YTC</scene>, <scene name='pdbligand=YTN:(3~{R},4~{R})-4-(1,3-benzodioxol-5-ylmethyl)-3-[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one'>YTN</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=YTC:(3~{S},4~{S})-4-(1,3-benzodioxol-5-ylmethyl)-3-[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one'>YTC</scene>, <scene name='pdbligand=YTN:(3~{R},4~{R})-4-(1,3-benzodioxol-5-ylmethyl)-3-[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one'>YTN</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=7e38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e38 OCA], [https://pdbe.org/7e38 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e38 RCSB], [https://www.ebi.ac.uk/pdbsum/7e38 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e38 ProSAT]</span></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=7e38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e38 OCA], [https://pdbe.org/7e38 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e38 RCSB], [https://www.ebi.ac.uk/pdbsum/7e38 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e38 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Function == | ||
| - | [https://www.uniprot.org/uniprot/2ODD_SINHE 2ODD_SINHE] | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Deoxypodophyllotoxin contains a core of four fused rings (A to D) with three consecutive chiral centers, the last being created by the attachment of a peripheral trimethoxyphenyl ring (E) to ring C. Previous studies have suggested that the iron(II)- and 2-oxoglutarate-dependent (Fe/2OG) oxygenase, deoxypodophyllotoxin synthase (DPS), catalyzes the oxidative coupling of ring B and ring E to form ring C and complete the tetracyclic core. Despite recent efforts to deploy DPS in the preparation of deoxypodophyllotoxin analogs, the mechanism underlying the regio- and stereoselectivity of this cyclization event has not been elucidated. Herein, we report 1) two structures of DPS in complex with 2OG and (+/-)-yatein, 2) in vitro analysis of enzymatic reactivity with substrate analogs, and 3) model reactions addressing DPS's catalytic mechanism. The results disfavor a prior proposal of on-pathway benzylic hydroxylation. Rather, the DPS-catalyzed cyclization likely proceeds by hydrogen atom abstraction from C7', oxidation of the benzylic radical to a carbocation, Friedel-Crafts-like ring closure, and rearomatization of ring B by C6 deprotonation. This mechanism adds to the known pathways for transformation of the carbon-centered radical in Fe/2OG enzymes and suggests what types of substrate modification are likely tolerable in DPS-catalyzed production of deoxypodophyllotoxin analogs. | ||
| - | |||
| - | Mechanistic analysis of carbon-carbon bond formation by deoxypodophyllotoxin synthase.,Tang H, Wu MH, Lin HY, Han MR, Tu YH, Yang ZJ, Chien TC, Chan NL, Chang WC Proc Natl Acad Sci U S A. 2022 Jan 4;119(1). pii: 2113770119. doi:, 10.1073/pnas.2113770119. PMID:34969844<ref>PMID:34969844</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 7e38" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Sinopodophyllum hexandrum]] | ||
[[Category: Chan N-L]] | [[Category: Chan N-L]] | ||
[[Category: Chang W-c]] | [[Category: Chang W-c]] | ||
[[Category: Chien T-C]] | [[Category: Chien T-C]] | ||
[[Category: Wu M-H]] | [[Category: Wu M-H]] | ||
Current revision
Crystal structure of deoxypodophyllotoxin synthase from Sinopodophyllum hexandrum in complex with yatein and succinate
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