5ybl

From Proteopedia

(Difference between revisions)

Revision as of 09:15, 21 October 2020

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

Structural highlights

5ybl is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rodriguez-Urra AB, Jimenez C, Nieto MI, Rodriguez J, Hayashi H, Ugalde U. Signaling the induction of sporulation involves the interaction of two secondary metabolites in Aspergillus nidulans. ACS Chem Biol. 2012 Mar 16;7(3):599-606. doi: 10.1021/cb200455u. Epub 2012 Jan, 24. PMID:22234162 doi:http://dx.doi.org/10.1021/cb200455u
↑ Lo HC, Entwistle R, Guo CJ, Ahuja M, Szewczyk E, Hung JH, Chiang YM, Oakley BR, Wang CC. Two separate gene clusters encode the biosynthetic pathway for the meroterpenoids austinol and dehydroaustinol in Aspergillus nidulans. J Am Chem Soc. 2012 Mar 14;134(10):4709-20. doi: 10.1021/ja209809t. Epub 2012 Feb, 29. PMID:22329759 doi:http://dx.doi.org/10.1021/ja209809t
↑ Matsuda Y, Awakawa T, Wakimoto T, Abe I. Spiro-ring formation is catalyzed by a multifunctional dioxygenase in austinol biosynthesis. J Am Chem Soc. 2013 Jul 31;135(30):10962-5. doi: 10.1021/ja405518u. Epub 2013 Jul, 22. PMID:23865690 doi:http://dx.doi.org/10.1021/ja405518u
↑ Nakashima Y, Mori T, Nakamura H, Awakawa T, Hoshino S, Senda M, Senda T, Abe I. Structure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis. Nat Commun. 2018 Jan 9;9(1):104. doi: 10.1038/s41467-017-02371-w. PMID:29317628 doi:http://dx.doi.org/10.1038/s41467-017-02371-w

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ybl"

Categories: Large Structures | Nakashima, Y | Senda, M | Alpha-kegoglutarate-dependent dioxygenase | Oxidoreductase

@@ Line 1: / Line 1: @@
 ==Fe(II)/(alpha)ketoglutarate-dependent dioxygenase AusE==
-<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 ==
-<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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YBL FirstGlance]. <br>
+<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>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=MN:MANGANESE+(II)+ION'>MN</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=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='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>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
 </div>
 <div class="pdbe-citations 5ybl" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Nakashima, Y]]
 [[Category: Senda, M]]
 [[Category: Alpha-kegoglutarate-dependent dioxygenase]]
 [[Category: Oxidoreductase]]

5ybl

From Proteopedia

Revision as of 09:15, 21 October 2020

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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