7oc6
From Proteopedia
(Difference between revisions)
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==Selenomethionine derivative of alpha-humulene synthase AsR6 from Sarocladium schorii== | ==Selenomethionine derivative of alpha-humulene synthase AsR6 from Sarocladium schorii== | ||
| - | <StructureSection load='7oc6' size='340' side='right'caption='[[7oc6]]' scene=''> | + | <StructureSection load='7oc6' size='340' side='right'caption='[[7oc6]], [[Resolution|resolution]] 2.01Å' 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=7OC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OC6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7oc6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Acremonium_strictum_(strain_imi_501407) Acremonium strictum (strain imi 501407)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OC6 FirstGlance]. <br> |
| - | </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=7oc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oc6 OCA], [https://pdbe.org/7oc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oc6 RCSB], [https://www.ebi.ac.uk/pdbsum/7oc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oc6 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">asR6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2203296 Acremonium strictum (strain IMI 501407)])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Alpha-humulene_synthase Alpha-humulene synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.104 4.2.3.104] </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=7oc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oc6 OCA], [https://pdbe.org/7oc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oc6 RCSB], [https://www.ebi.ac.uk/pdbsum/7oc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oc6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/ASR6_SARSH ASR6_SARSH]] Alpha-humulene synthase; part of the gene cluster that mediates the biosynthesis of xenovulene A, an unusual meroterpenoid that has potent inhibitory effects on the human gamma-aminobutyrate A (GABAA) benzodiazepine receptor (PubMed:29773797). The first step of xenovulene A biosynthesis is the biosynthesis of 3-methylorcinaldehyde performed by the non-reducing polyketide synthase aspks1 (PubMed:17912413, PubMed:29773797, PubMed:20552126). The salicylate hydroxylase asL1 then catalyzes the oxidative dearomatization of 3-methylorcinaldehyde to yield a dearomatized hydroxycyclohexadione (PubMed:29773797). The 2-oxoglutarate-dependent dioxygenase asL3 further catalyzes the oxidative ring expansion to provide the first tropolone metabolite (PubMed:29773797). The cytochrome P450 monooxygenase asR2 allows the synthesis of tropolone hemiacetal (PubMed:29773797). In parallel, a previously unrecognised class of terpene cyclase, asR6, produces alpha-humulene from farnesylpyrophosphate (FPP) (PubMed:29773797). The putative Diels-Alderase asR5 probably catalyzes the formation of the tropolone-humulene skeleton by linking humulene and the polyketide moiety (PubMed:29773797). Oxidative-ring contractions catalyzed by asL4 and asL6 then processively remove carbon atoms from the polyketide to yield xenovulene A (PubMed:29773797).<ref>PMID:17912413</ref> <ref>PMID:20552126</ref> <ref>PMID:29773797</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The non-canonical terpene cyclase AsR6 is responsible for the formation of 2E,6E,9E-humulene during the biosynthesis of the tropolone sesquiterpenoid (TS) xenovulene A. The structures of unliganded AsR6 and of AsR6 in complex with an in crystallo cyclized reaction product and thiolodiphosphate reveal a new farnesyl diphosphate binding motif that comprises a unique binuclear Mg2+cluster and an essential K289 residue that is conserved in all humulene synthases involved in TS formation. Structure-based sitedirected mutagenesis of AsR6 and its homologue EupR3 identify a single residue, L285/M261, that controls the production of either 2E,6E,9E- or 2Z,6E,9E-humulene. A possible mechanism for the observed stereoselectivity was investigated using different isoprenoid precursors and results demonstrate that M261 has gatekeeping control over product formation. | ||
| + | |||
| + | Understanding and Engineering the Stereoselectivity of Humulene Synthase.,Schotte C, Lukat P, Deuschmann A, Blankenfeldt W, Cox RJ Angew Chem Int Ed Engl. 2021 Jun 28. doi: 10.1002/anie.202106718. PMID:34180566<ref>PMID:34180566</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7oc6" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Alpha-humulene synthase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Blankenfeldt W]] | + | [[Category: Blankenfeldt, W]] |
| - | [[Category: Cox | + | [[Category: Cox, R J]] |
| - | [[Category: Deuschmann A]] | + | [[Category: Deuschmann, A]] |
| - | [[Category: Lukat P]] | + | [[Category: Lukat, P]] |
| - | [[Category: Schotte C]] | + | [[Category: Schotte, C]] |
| + | [[Category: 2e-humulene]] | ||
| + | [[Category: Alpha-humulene]] | ||
| + | [[Category: Biosynthetic protein]] | ||
| + | [[Category: Cyclase]] | ||
| + | [[Category: Humulene]] | ||
| + | [[Category: Terpene cyclase]] | ||
| + | [[Category: Tropolone sesquiterpenoid]] | ||
| + | [[Category: Xenovulene]] | ||
Revision as of 09:39, 15 September 2021
Selenomethionine derivative of alpha-humulene synthase AsR6 from Sarocladium schorii
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