5ybl: Difference between revisions

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<StructureSection load='5ybl' size='340' side='right'caption='[[5ybl]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
<StructureSection load='5ybl' size='340' side='right'caption='[[5ybl]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5ybl]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YBL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5YBL FirstGlance]. <br>
<table><tr><td colspan='2'>[[5ybl]] is a 4 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=5YBL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YBL 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=MN:MANGANESE+(II)+ION'>MN</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]] 2.108&#8491;</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=5ybl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ybl OCA], [http://pdbe.org/5ybl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ybl RCSB], [http://www.ebi.ac.uk/pdbsum/5ybl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ybl ProSAT]</span></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=MN:MANGANESE+(II)+ION'>MN</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=5ybl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ybl OCA], [https://pdbe.org/5ybl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ybl RCSB], [https://www.ebi.ac.uk/pdbsum/5ybl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ybl ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/AUSE_EMENI AUSE_EMENI]] Dioxygenase; part of the gene cluster B that mediates the biosynthesis of austinol and dehydroaustinol, two fungal meroterpenoids (PubMed:22329759). The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:22329759). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:22329759). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (PubMed:22329759). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (PubMed:22329759, PubMed:23865690). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (PubMed:22329759). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (PubMed:22329759). Finally, the cytochrome P450 monooxygenase ausG modifies austinolide to austinol (PubMed:22329759). Austinol can be further modified to dehydroaustinol which forms a diffusible complex with diorcinol that initiates conidiation (PubMed:22234162, PubMed:22329759). AusE catalyzes various oxidation reactions in addition to spiro-ring formation and works iteratively in the biosynthetic process to produce shunt products such as 5-hydroxyberkeleyone, preaustinoid C and austinoid C (PubMed:23865690).<ref>PMID:22234162</ref> <ref>PMID:22329759</ref> <ref>PMID:23865690</ref> 
[https://www.uniprot.org/uniprot/AUSE_EMENI AUSE_EMENI] Dioxygenase; part of the gene cluster B that mediates the biosynthesis of austinol and dehydroaustinol, two fungal meroterpenoids (PubMed:22329759). The first step of the pathway is the synthesis of 3,5-dimethylorsellinic acid by the polyketide synthase ausA (PubMed:22329759). 3,5-dimethylorsellinic acid is then prenylated by the polyprenyl transferase ausN (PubMed:22329759). Further epoxidation by the FAD-dependent monooxygenase ausM and cyclization by the probable terpene cyclase ausL lead to the formation of protoaustinoid A (PubMed:22329759). Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by the combined action of the FAD-binding monooxygenases ausB and ausC, and the dioxygenase ausE (PubMed:22329759, PubMed:23865690). Acid-catalyzed keto-rearrangement and ring contraction of the tetraketide portion of preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (PubMed:22329759). The aldo-keto reductase ausK, with the help of ausH, is involved in the next step by transforming preaustinoid A4 into isoaustinone which is in turn hydroxylated by the P450 monooxygenase ausI to form austinolide (PubMed:22329759). Finally, the cytochrome P450 monooxygenase ausG modifies austinolide to austinol (PubMed:22329759). Austinol can be further modified to dehydroaustinol which forms a diffusible complex with diorcinol that initiates conidiation (PubMed:22234162, PubMed:22329759). AusE catalyzes various oxidation reactions in addition to spiro-ring formation and works iteratively in the biosynthetic process to produce shunt products such as 5-hydroxyberkeleyone, preaustinoid C and austinoid C (PubMed:23865690).<ref>PMID:22234162</ref> <ref>PMID:22329759</ref> <ref>PMID:23865690</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Non-heme iron and alpha-ketoglutarate (alphaKG) oxygenases catalyze remarkably diverse reactions using a single ferrous ion cofactor. A major challenge in studying this versatile family of enzymes is to understand their structure-function relationship. AusE from Aspergillus nidulans and PrhA from Penicillium brasilianum are two highly homologous Fe(II)/alphaKG oxygenases in fungal meroterpenoid biosynthetic pathways that use preaustinoid A1 as a common substrate to catalyze divergent rearrangement reactions to form the spiro-lactone in austinol and cycloheptadiene moiety in paraherquonin, respectively. Herein, we report the comparative structural study of AusE and PrhA, which led to the identification of three key active site residues that control their reactivity. Structure-guided mutagenesis of these residues results in successful interconversion of AusE and PrhA functions as well as generation of the PrhA double and triple mutants with expanded catalytic repertoire. Manipulation of the multifunctional Fe(II)/alphaKG oxygenases thus provides an excellent platform for the future development of biocatalysts.
 
Structure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis.,Nakashima Y, Mori T, Nakamura H, Awakawa T, Hoshino S, Senda M, Senda T, Abe I Nat Commun. 2018 Jan 9;9(1):104. doi: 10.1038/s41467-017-02371-w. PMID:29317628<ref>PMID:29317628</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ybl" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Aspergillus nidulans FGSC A4]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Nakashima, Y]]
[[Category: Nakashima Y]]
[[Category: Senda, M]]
[[Category: Senda M]]
[[Category: Alpha-kegoglutarate-dependent dioxygenase]]
[[Category: Oxidoreductase]]

Latest revision as of 10:22, 27 March 2024

Fe(II)/(alpha)ketoglutarate-dependent dioxygenase AusE

5ybl, resolution 2.11Å

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