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| | <StructureSection load='5dap' size='340' side='right'caption='[[5dap]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='5dap' size='340' side='right'caption='[[5dap]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dap]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_nidulans Aspergillus nidulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DAP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DAP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dap]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_nidulans_FGSC_A4 Aspergillus nidulans FGSC A4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DAP FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nao|4nao]]</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=5dap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dap OCA], [https://pdbe.org/5dap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dap RCSB], [https://www.ebi.ac.uk/pdbsum/5dap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dap ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AN9227.2, ANIA_09227 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227321 Aspergillus nidulans])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5dap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dap OCA], [http://pdbe.org/5dap PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dap RCSB], [http://www.ebi.ac.uk/pdbsum/5dap PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dap ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/ASQJ_EMENI ASQJ_EMENI] Iron/alpha-ketoglutarate-dependent dioxygenase; part of the gene cluster that mediates the biosynthesis of the aspoquinolone mycotoxins (PubMed:25251934, PubMed:26553478). The first stage is catalyzed by the nonribosomal pepdide synthetase asqK that condenses anthranilic acid and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin (PubMed:25251934). AsqK is also able to use anthranilic acid and L-phenylalanine as substrates to produce cyclopeptin, but at a tenfold lower rate (PubMed:25251934). 4'-methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by the ketoglutarate-dependent dioxygenase asqJ through dehydrogenation to form a double bond between C-alpha and C-beta of the O-methyltyrosine side chain (PubMed:25251934, PubMed:26553478). AsqJ also converts its first product 4'-methoxydehydrocyclopeptin to 4'-methoxycyclopenin (PubMed:25251934). AsqJ is a very unique dioxygenase which is capable of catalyzing radical-mediated dehydrogenation and epoxidation reactions sequentially on a 6,7-benzo-diazepinedione substrate in the 4'-methoxyviridicatin biosynthetic pathway (PubMed:25251934). The following conversion of 4'-methoxycyclopenin into 4'-methoxyviridicatin proceeds non-enzymatically (PubMed:25251934). AsqJ is also capable of converting cyclopeptin into dehydrocyclopeptin and cyclopenin in a sequential fashion (PubMed:25251934). Cyclopenin can be converted into viridicatin non-enzymatically (PubMed:25251934). 4'-methoxyviridicatin likely acts as a precursor of quinolone natural products, such as aspoquinolones, peniprequinolones, penigequinolones, and yaequinolones (PubMed:25251934). Further characterization of the remaining genes in the cluster has still to be done to determine the exact identity of quinolone products this cluster is responsible for biosynthesizing (PubMed:25251934).<ref>PMID:25251934</ref> <ref>PMID:26553478</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 18: |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5dap" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5dap" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Dioxygenase 3D structures|Dioxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aspergillus nidulans]] | + | [[Category: Aspergillus nidulans FGSC A4]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Braeuer, A]] | + | [[Category: Braeuer A]] |
| - | [[Category: Groll, M]] | + | [[Category: Groll M]] |
| - | [[Category: Alkaloid]]
| + | |
| - | [[Category: Antibiotic]]
| + | |
| - | [[Category: Biosynthesis]]
| + | |
| - | [[Category: Desaturase]]
| + | |
| - | [[Category: Epoxidase]]
| + | |
| - | [[Category: Fragmentation]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Viridicatin]]
| + | |
| Structural highlights
Function
ASQJ_EMENI Iron/alpha-ketoglutarate-dependent dioxygenase; part of the gene cluster that mediates the biosynthesis of the aspoquinolone mycotoxins (PubMed:25251934, PubMed:26553478). The first stage is catalyzed by the nonribosomal pepdide synthetase asqK that condenses anthranilic acid and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin (PubMed:25251934). AsqK is also able to use anthranilic acid and L-phenylalanine as substrates to produce cyclopeptin, but at a tenfold lower rate (PubMed:25251934). 4'-methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by the ketoglutarate-dependent dioxygenase asqJ through dehydrogenation to form a double bond between C-alpha and C-beta of the O-methyltyrosine side chain (PubMed:25251934, PubMed:26553478). AsqJ also converts its first product 4'-methoxydehydrocyclopeptin to 4'-methoxycyclopenin (PubMed:25251934). AsqJ is a very unique dioxygenase which is capable of catalyzing radical-mediated dehydrogenation and epoxidation reactions sequentially on a 6,7-benzo-diazepinedione substrate in the 4'-methoxyviridicatin biosynthetic pathway (PubMed:25251934). The following conversion of 4'-methoxycyclopenin into 4'-methoxyviridicatin proceeds non-enzymatically (PubMed:25251934). AsqJ is also capable of converting cyclopeptin into dehydrocyclopeptin and cyclopenin in a sequential fashion (PubMed:25251934). Cyclopenin can be converted into viridicatin non-enzymatically (PubMed:25251934). 4'-methoxyviridicatin likely acts as a precursor of quinolone natural products, such as aspoquinolones, peniprequinolones, penigequinolones, and yaequinolones (PubMed:25251934). Further characterization of the remaining genes in the cluster has still to be done to determine the exact identity of quinolone products this cluster is responsible for biosynthesizing (PubMed:25251934).[1] [2]
Publication Abstract from PubMed
Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The FeII /alpha-ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4'-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase.
Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis.,Brauer A, Beck P, Hintermann L, Groll M Angew Chem Int Ed Engl. 2015 Nov 10. doi: 10.1002/anie.201507835. PMID:26553478[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ishikawa N, Tanaka H, Koyama F, Noguchi H, Wang CC, Hotta K, Watanabe K. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew Chem Int Ed Engl. 2014 Nov 17;53(47):12880-4. doi: 10.1002/anie.201407920. , Epub 2014 Sep 22. PMID:25251934 doi:http://dx.doi.org/10.1002/anie.201407920
- ↑ Brauer A, Beck P, Hintermann L, Groll M. Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis. Angew Chem Int Ed Engl. 2015 Nov 10. doi: 10.1002/anie.201507835. PMID:26553478 doi:http://dx.doi.org/10.1002/anie.201507835
- ↑ Brauer A, Beck P, Hintermann L, Groll M. Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis. Angew Chem Int Ed Engl. 2015 Nov 10. doi: 10.1002/anie.201507835. PMID:26553478 doi:http://dx.doi.org/10.1002/anie.201507835
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