6cqb: Difference between revisions
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==Crystal Structure of Piper methysticum Chalcone Synthase== | ==Crystal Structure of Piper methysticum Chalcone Synthase== | ||
<StructureSection load='6cqb' size='340' side='right' caption='[[6cqb]], [[Resolution|resolution]] 2.91Å' scene=''> | <StructureSection load='6cqb' size='340' side='right'caption='[[6cqb]], [[Resolution|resolution]] 2.91Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6cqb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CQB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CQB FirstGlance]. <br> | <table><tr><td colspan='2'>[[6cqb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Piper_methysticum Piper methysticum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CQB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CQB FirstGlance]. <br> | ||
</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=6cqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cqb OCA], [http://pdbe.org/6cqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cqb RCSB], [http://www.ebi.ac.uk/pdbsum/6cqb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cqb ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=130404 Piper methysticum])</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=6cqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cqb OCA], [http://pdbe.org/6cqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cqb RCSB], [http://www.ebi.ac.uk/pdbsum/6cqb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cqb ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:31332312</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6cqb" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Piper methysticum]] | |||
[[Category: Pluskal, T]] | [[Category: Pluskal, T]] | ||
[[Category: Weng, J K]] | [[Category: Weng, J K]] | ||
Revision as of 09:13, 7 August 2019
Crystal Structure of Piper methysticum Chalcone SynthaseCrystal Structure of Piper methysticum Chalcone Synthase
Structural highlights
Publication Abstract from PubMedKava (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
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