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| | <StructureSection load='6kjg' size='340' side='right'caption='[[6kjg]], [[Resolution|resolution]] 1.99Å' scene=''> | | <StructureSection load='6kjg' size='340' side='right'caption='[[6kjg]], [[Resolution|resolution]] 1.99Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6kjg]] is a 3 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=6KJG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KJG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6kjg]] is a 3 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=6KJG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KJG FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">psoF, AFUA_8G00440 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=330879 ASPFU])</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]] 1.99Å</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=6kjg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kjg OCA], [http://pdbe.org/6kjg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kjg RCSB], [http://www.ebi.ac.uk/pdbsum/6kjg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kjg 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=6kjg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kjg OCA], [https://pdbe.org/6kjg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kjg RCSB], [https://www.ebi.ac.uk/pdbsum/6kjg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kjg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PSOF_ASPFU PSOF_ASPFU]] Dual-functional monooxygenase/methyltransferase; 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). 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> | + | [https://www.uniprot.org/uniprot/PSOF_ASPFU PSOF_ASPFU] Dual-functional monooxygenase/methyltransferase; 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). 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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aspfu]] | + | [[Category: Aspergillus fumigatus Af293]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hara, K]] | + | [[Category: Hara K]] |
| - | [[Category: Hashimoto, H]] | + | [[Category: Hashimoto H]] |
| - | [[Category: Matsushita, T]] | + | [[Category: Matsushita T]] |
| - | [[Category: Tsunematsu, Y]] | + | [[Category: Tsunematsu Y]] |
| - | [[Category: Watanabe, K]] | + | [[Category: Watanabe K]] |
| - | [[Category: Metyltransferase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
PSOF_ASPFU Dual-functional monooxygenase/methyltransferase; 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). 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]
Publication Abstract from PubMed
Biosynthesis of certain fungal polyketide-peptide synthetases involves C-methyltransferase activity that adds one or more S-adenosyl-l-methionine-derived methyl groups to the carbon framework. The previously reported PsoF-MT, the stand-alone C-methyltransferase (MT) from the pseurotin biosynthetic pathway that exists as a domain within a trifunctional didomain enzyme PsoF, was characterized crystallographically and kinetically using mutants with substrate analogs to understand how a trans-acting C-MT works and compare it to known polyketide synthase-associated C-MTs. This study identified key active-site residues involved in catalysis and substrate recognition, which led us to propose the mechanism of C-methylation and substrate specificity determinants in PsoF-MT.
Functional and Structural Analyses of trans C-Methyltransferase in Fungal Polyketide Biosynthesis.,Kishimoto S, Tsunematsu Y, Matsushita T, Hara K, Hashimoto H, Tang Y, Watanabe K Biochemistry. 2019 Sep 24;58(38):3933-3937. doi: 10.1021/acs.biochem.9b00702., Epub 2019 Sep 11. PMID:31486637[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Kishimoto S, Tsunematsu Y, Matsushita T, Hara K, Hashimoto H, Tang Y, Watanabe K. Functional and Structural Analyses of trans C-Methyltransferase in Fungal Polyketide Biosynthesis. Biochemistry. 2019 Sep 24;58(38):3933-3937. doi: 10.1021/acs.biochem.9b00702., Epub 2019 Sep 11. PMID:31486637 doi:http://dx.doi.org/10.1021/acs.biochem.9b00702
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