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5x9k

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Current revision

Structure of AusH from Aspergillus nidulans

Structural highlights

5x9k is a 2 chain structure with sequence from Aspergillus nidulans FGSC A4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.798Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AUSH_EMENI Austinol synthesis protein H: 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). AusH may play a role in the altering of ausK's stereospecificity to produce isoaustinone instead of the shunt product (5'R)-isoaustinone (PubMed:22329759).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Trt14 from Aspergillus terreus is involved in unusual skeletal reconstruction during the biosynthesis of the fungal meroterpenoid terretonin. Detailed in vitro characterization revealed that this novel multifunctional enzyme catalyzes not only the D-ring expansion via intramolecular methoxy rearrangement, but also the hydrolysis of the expanded D-ring. The X-ray crystal structures of Trt14, in complex with substrate or product, and two Trt14 homologs, AusH and PrhC from Aspergillus nidulans and Penicillium brasilianum, respectively, indicated similar overall structures to those of the NTF2-like superfamily of enzymes, despite lacking sequence and functional similarities. Moreover, we gained structural insight into the mechanism of the Trt14-catalyzed ring reconstruction from the in-crystal enzyme reaction and site-directed mutagenesis to show that this reaction involves sequential ester bond cleavage and formation. Structural comparison of Trt14 and its homologs suggests that the enzymes in this new superfamily employ similar acid-base chemistry to diversify the molecular architecture of fungal meroterpenoids.

Molecular basis for the unusual ring reconstruction in fungal meroterpenoid biogenesis.,Mori T, Iwabuchi T, Hoshino S, Wang H, Matsuda Y, Abe I Nat Chem Biol. 2017 Oct;13(10):1066-1073. doi: 10.1038/nchembio.2443. Epub 2017, Jul 31. PMID:28759016^[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
↑ Mori T, Iwabuchi T, Hoshino S, Wang H, Matsuda Y, Abe I. Molecular basis for the unusual ring reconstruction in fungal meroterpenoid biogenesis. Nat Chem Biol. 2017 Oct;13(10):1066-1073. doi: 10.1038/nchembio.2443. Epub 2017, Jul 31. PMID:28759016 doi:http://dx.doi.org/10.1038/nchembio.2443

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5x9k"

Categories: Aspergillus nidulans FGSC A4 | Large Structures | Abe I | Iwabuchi T | Matsuda Y

@@ Line 3: / Line 3: @@
 <StructureSection load='5x9k' size='340' side='right'caption='[[5x9k]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5x9k]] is a 2 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=5X9K OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5X9K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5x9k]] is a 2 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=5X9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X9K FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ausH, AN9249 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227321 Aspergillus nidulans])</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]] 1.798&#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=5x9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x9k OCA], [http://pdbe.org/5x9k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x9k RCSB], [http://www.ebi.ac.uk/pdbsum/5x9k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x9k 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=5x9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x9k OCA], [https://pdbe.org/5x9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x9k RCSB], [https://www.ebi.ac.uk/pdbsum/5x9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x9k ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/AUSH_EMENI AUSH_EMENI]] Austinol synthesis protein H: 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). AusH may play a role in the altering of ausK's stereospecificity to produce isoaustinone instead of the shunt product (5'R)-isoaustinone (PubMed:22329759).<ref>PMID:22234162</ref> <ref>PMID:22329759</ref> <ref>PMID:23865690</ref>
+[https://www.uniprot.org/uniprot/AUSH_EMENI AUSH_EMENI] Austinol synthesis protein H: 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). AusH may play a role in the altering of ausK's stereospecificity to produce isoaustinone instead of the shunt product (5'R)-isoaustinone (PubMed:22329759).<ref>PMID:22234162</ref> <ref>PMID:22329759</ref> <ref>PMID:23865690</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Aspergillus nidulans]]
+[[Category: Aspergillus nidulans FGSC A4]]
 [[Category: Large Structures]]
-[[Category: Abe, I]]
+[[Category: Abe I]]
-[[Category: Iwabuchi, T]]
+[[Category: Iwabuchi T]]
-[[Category: Matsuda, Y]]
+[[Category: Matsuda Y]]
-[[Category: Austinol]]
-[[Category: Isomerase]]
-[[Category: Meroterpenoid]]

5x9k

From Proteopedia

Current revision

Structure of AusH from Aspergillus nidulans

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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