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| | ==Crystallographic Structure of PsoE with Co== | | ==Crystallographic Structure of PsoE with Co== |
| - | <StructureSection load='5f8b' size='340' side='right' caption='[[5f8b]], [[Resolution|resolution]] 2.54Å' scene=''> | + | <StructureSection load='5f8b' size='340' side='right'caption='[[5f8b]], [[Resolution|resolution]] 2.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5f8b]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspfu Aspfu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F8B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F8B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5f8b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus_Af293 Aspergillus fumigatus Af293]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F8B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F8B FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=PZS:(5~{S},8~{S},9~{R})-2-[(~{E})-HEX-1-ENYL]-8-METHOXY-3-METHYL-9-OXIDANYL-8-(PHENYLCARBONYL)-1-OXA-7-AZASPIRO[4.4]NON-2-ENE-4,6-DIONE'>PZS</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]] 2.54Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AFUA_8G00580 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=330879 ASPFU])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=PZS:(5~{S},8~{S},9~{R})-2-[(~{E})-HEX-1-ENYL]-8-METHOXY-3-METHYL-9-OXIDANYL-8-(PHENYLCARBONYL)-1-OXA-7-AZASPIRO[4.4]NON-2-ENE-4,6-DIONE'>PZS</scene></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=5f8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f8b OCA], [http://pdbe.org/5f8b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f8b RCSB], [http://www.ebi.ac.uk/pdbsum/5f8b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f8b 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=5f8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f8b OCA], [https://pdbe.org/5f8b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f8b RCSB], [https://www.ebi.ac.uk/pdbsum/5f8b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f8b ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/PSOE_ASPFU PSOE_ASPFU] Glutathione S-transferase; part of the gene cluster that mediates the biosynthesis of pseurotin A, a competitive inhibitor of chitin synthase and an inducer of nerve-cell proliferation (PubMed:24082142, PubMed:24939566). The PKS-NRPS hybrid synthetase psoA is responsible for the biosynthesis of azaspirene, one of the first intermediates having the 1-oxa-7-azaspiro[4,4]-non-2-ene-4,6-dione core of pseurotin, via condensation of one acetyl-CoA, 4 malonyl-CoA, and a L-phenylalanine molecule (PubMed:24082142, PubMed:24939566). The dual-functional monooxygenase/methyltransferase psoF seems to be involved in the addition of the C3 methyl group onto the pseurotin scaffold (PubMed:24939566). Azaspirene is then converted to synerazol through 4 steps including oxidation of C17 by the cytochrome P450 monooxygenase psoD, O-methylation of the hydroxy group of C8 by the methyltransferase psoC, and the trans-to-cis isomerization of the C13 olefin by the glutathione S-transferase psoE (PubMed:24939566, PubMed:27072782). The fourth step of synerazol production is performed by the dual-functional monooxygenase/methyltransferase psoF which seems to catalyze the epoxidation of the intermediate deepoxy-synerazol (PubMed:24939566). Synerazol can be attacked by a water molecule nonenzymatically at two different positions to yield two diol products, pseurotin A and pseurotin D (PubMed:24939566).<ref>PMID:24082142</ref> <ref>PMID:24939566</ref> <ref>PMID:27072782</ref> |
| - | Geometric isomerization can expand the scope of biological activities of natural products. The observed chemical diversity among the pseurotin-type fungal secondary metabolites is in part generated by a trans to cis isomerization of an olefin. In vitro characterizations of pseurotin biosynthetic enzymes revealed that the glutathione S-transferase PsoE requires participation of the bifunctional C-methyltransferase/epoxidase PsoF to complete the trans to cis isomerization of the pathway intermediate presynerazol. The crystal structure of the PsoE/glutathione/presynerazol complex indicated stereospecific glutathione-presynerazol conjugate formation is the principal function of PsoE. Moreover, PsoF was identified to have an additional, unexpected oxidative isomerase activity, thus making it a trifunctional enzyme which is key to the complexity generation in pseurotin biosynthesis. Through the study, we identified a novel mechanism of accomplishing a seemingly simple trans to cis isomerization reaction.
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| - | Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis.,Yamamoto T, Tsunematsu Y, Hara K, Suzuki T, Kishimoto S, Kawagishi H, Noguchi H, Hashimoto H, Tang Y, Hotta K, Watanabe K Angew Chem Int Ed Engl. 2016 May 17;55(21):6207-10. doi: 10.1002/anie.201600940. , Epub 2016 Apr 13. PMID:27072782<ref>PMID:27072782</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 5f8b" style="background-color:#fffaf0;"></div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aspfu]] | + | [[Category: Aspergillus fumigatus Af293]] |
| - | [[Category: Hara, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Hashimoto, H]] | + | [[Category: Hara K]] |
| - | [[Category: Tsunematsu, Y]] | + | [[Category: Hashimoto H]] |
| - | [[Category: Watanabe, K]] | + | [[Category: Tsunematsu Y]] |
| - | [[Category: Yamamoto, T]] | + | [[Category: Watanabe K]] |
| - | [[Category: Gst]]
| + | [[Category: Yamamoto T]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PSOE_ASPFU Glutathione S-transferase; part of the gene cluster that mediates the biosynthesis of pseurotin A, a competitive inhibitor of chitin synthase and an inducer of nerve-cell proliferation (PubMed:24082142, PubMed:24939566). The PKS-NRPS hybrid synthetase psoA is responsible for the biosynthesis of azaspirene, one of the first intermediates having the 1-oxa-7-azaspiro[4,4]-non-2-ene-4,6-dione core of pseurotin, via condensation of one acetyl-CoA, 4 malonyl-CoA, and a L-phenylalanine molecule (PubMed:24082142, PubMed:24939566). The dual-functional monooxygenase/methyltransferase psoF seems to be involved in the addition of the C3 methyl group onto the pseurotin scaffold (PubMed:24939566). Azaspirene is then converted to synerazol through 4 steps including oxidation of C17 by the cytochrome P450 monooxygenase psoD, O-methylation of the hydroxy group of C8 by the methyltransferase psoC, and the trans-to-cis isomerization of the C13 olefin by the glutathione S-transferase psoE (PubMed:24939566, PubMed:27072782). The fourth step of synerazol production is performed by the dual-functional monooxygenase/methyltransferase psoF which seems to catalyze the epoxidation of the intermediate deepoxy-synerazol (PubMed:24939566). Synerazol can be attacked by a water molecule nonenzymatically at two different positions to yield two diol products, pseurotin A and pseurotin D (PubMed:24939566).[1] [2] [3]
References
- ↑ Wiemann P, Guo CJ, Palmer JM, Sekonyela R, Wang CC, Keller NP. Prototype of an intertwined secondary-metabolite supercluster. Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):17065-70. doi:, 10.1073/pnas.1313258110. Epub 2013 Sep 30. PMID:24082142 doi:http://dx.doi.org/10.1073/pnas.1313258110
- ↑ Tsunematsu Y, Fukutomi M, Saruwatari T, Noguchi H, Hotta K, Tang Y, Watanabe K. Elucidation of pseurotin biosynthetic pathway points to trans-acting C-methyltransferase: generation of chemical diversity. Angew Chem Int Ed Engl. 2014 Aug 4;53(32):8475-9. doi: 10.1002/anie.201404804., Epub 2014 Jun 18. PMID:24939566 doi:http://dx.doi.org/10.1002/anie.201404804
- ↑ Yamamoto T, Tsunematsu Y, Hara K, Suzuki T, Kishimoto S, Kawagishi H, Noguchi H, Hashimoto H, Tang Y, Hotta K, Watanabe K. Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis. Angew Chem Int Ed Engl. 2016 May 17;55(21):6207-10. doi: 10.1002/anie.201600940. , Epub 2016 Apr 13. PMID:27072782 doi:http://dx.doi.org/10.1002/anie.201600940
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