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| | <StructureSection load='6op5' size='340' side='right'caption='[[6op5]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='6op5' size='340' side='right'caption='[[6op5]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6op5]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Piper_methysticum Piper methysticum]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6co0 6co0]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OP5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OP5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6op5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Piper_methysticum Piper methysticum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OP5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=WCA:P-COUMAROYL-COA'>WCA</scene></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]] 2.7Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=60F:(2~{R})-2-AZANYL-3-[(~{E})-3-(4-HYDROXYPHENYL)PROP-2-ENOYL]SULFANYL-PROPANOIC+ACID'>60F</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=60F:(2~{R})-2-AZANYL-3-[(~{E})-3-(4-HYDROXYPHENYL)PROP-2-ENOYL]SULFANYL-PROPANOIC+ACID'>60F</scene>, <scene name='pdbligand=WCA:P-COUMAROYL-COA'>WCA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6cqb|6cqb]], [[6nbr|6nbr]]</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=6op5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6op5 OCA], [https://pdbe.org/6op5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6op5 RCSB], [https://www.ebi.ac.uk/pdbsum/6op5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6op5 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6op5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6op5 OCA], [http://pdbe.org/6op5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6op5 RCSB], [http://www.ebi.ac.uk/pdbsum/6op5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6op5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A384E132_9MAGN A0A384E132_9MAGN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Piper methysticum]] | | [[Category: Piper methysticum]] |
| - | [[Category: Pluskal, T]] | + | [[Category: Pluskal T]] |
| - | [[Category: Weng, J K]] | + | [[Category: Weng JK]] |
| - | [[Category: Kavalactone biosynthesis]]
| + | |
| - | [[Category: Phenylpropanoid pathway]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
A0A384E132_9MAGN
Publication Abstract from PubMed
Kava (Piper methysticum) is an ethnomedicinal shrub native to the Polynesian islands with well-established anxiolytic and analgesic properties. Its main psychoactive principles, kavalactones, form a unique class of polyketides that interact with the human central nervous system through mechanisms distinct from those of conventional psychiatric drugs. However, an unknown biosynthetic machinery and difficulty in chemical synthesis hinder the therapeutic use of kavalactones. In addition, kava also produces flavokavains, which are chalconoids with anticancer properties structurally related to kavalactones. Here, we report de novo elucidation of the key enzymes of the kavalactone and flavokavain biosynthetic network. We present the structural basis for the evolutionary development of a pair of paralogous styrylpyrone synthases that establish the kavalactone scaffold and the catalytic mechanism of a regio- and stereo-specific kavalactone reductase that produces a subset of chiral kavalactones. We further demonstrate the feasibility of engineering styrylpyrone production in heterologous hosts, thus opening a way to develop kavalactone-based non-addictive psychiatric therapeutics through synthetic biology.
The biosynthetic origin of psychoactive kavalactones in kava.,Pluskal T, Torrens-Spence MP, Fallon TR, De Abreu A, Shi CH, Weng JK Nat Plants. 2019 Jul 22. pii: 10.1038/s41477-019-0474-0. doi:, 10.1038/s41477-019-0474-0. PMID:31332312[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pluskal T, Torrens-Spence MP, Fallon TR, De Abreu A, Shi CH, Weng JK. The biosynthetic origin of psychoactive kavalactones in kava. Nat Plants. 2019 Jul 22. pii: 10.1038/s41477-019-0474-0. doi:, 10.1038/s41477-019-0474-0. PMID:31332312 doi:http://dx.doi.org/10.1038/s41477-019-0474-0
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