6ka2: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of a Thebaine synthase from Papaver somniferum in complex with TBN== | ==Crystal structure of a Thebaine synthase from Papaver somniferum in complex with TBN== | ||
<StructureSection load='6ka2' size='340' side='right'caption='[[6ka2]]' scene=''> | <StructureSection load='6ka2' size='340' side='right'caption='[[6ka2]], [[Resolution|resolution]] 2.35Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KA2 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6ka2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Papaver_somniferum Papaver somniferum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KA2 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D4R:(4R,7aR,12bS)-7,9-dimethoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline'>D4R</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=6ka2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ka2 OCA], [https://pdbe.org/6ka2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ka2 RCSB], [https://www.ebi.ac.uk/pdbsum/6ka2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ka2 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/THS2_PAPSO THS2_PAPSO] Catalyzes the formation of thebaine from (7S)-salutaridinol 7-O-acetate at the expense of labile hydroxylated by-products, which are preferentially produced by spontaneous allylic elimination. No visible activity toward (7S)-salutaridinol (at pH 7).<ref>PMID:29807982</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Thebaine synthase 2 (THS2) that can transform (7S)-salutaridinol 7-O-acetate to thebaine catalyzes the final step of thebaine biosynthesis in Papaver somniferum. Here, the crystal structures of THS2 and its complex with thebaine are reported, revealing the interaction network in the substrate-binding pocket. Subsequent docking and QM/MM studies was performed to further explore the catalytic mechanism of THS2. Our results suggest that T105 may abstract the proton of C4-OH from the substrate under the assistance of H89. The resulting C4-O(-) phenolate anion then attacks the nearby C5, and triggers intramolecular SN2' syn displacement with the elimination of O-acetyl group. Moreover, the latter SN2' reaction is the rate-determining step of the whole enzymatic reaction with an overall energy barrier of 18.8 kcal/mol. These findings are of pivotal importance to understand the mechanism of action of thebaine biosynthesis, and would guide enzyme engineering to enhance the production of opiate alkaloids via metabolic engineering. | |||
Structural insights into thebaine synthase 2 catalysis.,Chen CC, Xue J, Peng W, Wang B, Zhang L, Liu W, Ko TP, Huang JW, Zhou S, Min J, Ma L, Dai L, Guo RT, Yu X Biochem Biophys Res Commun. 2020 Aug 20;529(2):156-161. doi:, 10.1016/j.bbrc.2020.05.199. Epub 2020 Jun 22. PMID:32703404<ref>PMID:32703404</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ka2" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Papaver somniferum]] | |||
[[Category: Chen CC]] | [[Category: Chen CC]] | ||
[[Category: Guo RT]] | [[Category: Guo RT]] | ||
Latest revision as of 13:28, 22 November 2023
Crystal structure of a Thebaine synthase from Papaver somniferum in complex with TBNCrystal structure of a Thebaine synthase from Papaver somniferum in complex with TBN
Structural highlights
FunctionTHS2_PAPSO Catalyzes the formation of thebaine from (7S)-salutaridinol 7-O-acetate at the expense of labile hydroxylated by-products, which are preferentially produced by spontaneous allylic elimination. No visible activity toward (7S)-salutaridinol (at pH 7).[1] Publication Abstract from PubMedThebaine synthase 2 (THS2) that can transform (7S)-salutaridinol 7-O-acetate to thebaine catalyzes the final step of thebaine biosynthesis in Papaver somniferum. Here, the crystal structures of THS2 and its complex with thebaine are reported, revealing the interaction network in the substrate-binding pocket. Subsequent docking and QM/MM studies was performed to further explore the catalytic mechanism of THS2. Our results suggest that T105 may abstract the proton of C4-OH from the substrate under the assistance of H89. The resulting C4-O(-) phenolate anion then attacks the nearby C5, and triggers intramolecular SN2' syn displacement with the elimination of O-acetyl group. Moreover, the latter SN2' reaction is the rate-determining step of the whole enzymatic reaction with an overall energy barrier of 18.8 kcal/mol. These findings are of pivotal importance to understand the mechanism of action of thebaine biosynthesis, and would guide enzyme engineering to enhance the production of opiate alkaloids via metabolic engineering. Structural insights into thebaine synthase 2 catalysis.,Chen CC, Xue J, Peng W, Wang B, Zhang L, Liu W, Ko TP, Huang JW, Zhou S, Min J, Ma L, Dai L, Guo RT, Yu X Biochem Biophys Res Commun. 2020 Aug 20;529(2):156-161. doi:, 10.1016/j.bbrc.2020.05.199. Epub 2020 Jun 22. PMID:32703404[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||