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| | <StructureSection load='4qnw' size='340' side='right'caption='[[4qnw]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4qnw' size='340' side='right'caption='[[4qnw]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qnw]] is a 1 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=4QNW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QNW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qnw]] is a 1 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=4QNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QNW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AFUA_2G17960, EasA, fgaOx3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=330879 ASPFU])</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=4qnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qnw OCA], [https://pdbe.org/4qnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qnw RCSB], [https://www.ebi.ac.uk/pdbsum/4qnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qnw ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Chanoclavine-I_aldehyde_reductase Chanoclavine-I aldehyde reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.100 1.3.1.100] </span></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=4qnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qnw OCA], [http://pdbe.org/4qnw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qnw RCSB], [http://www.ebi.ac.uk/pdbsum/4qnw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qnw ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/EASA_ASPFU EASA_ASPFU] Aldehyde reductase; part of the gene cluster that mediates the biosynthesis of fumiclavanine C, a fungal ergot alkaloid (PubMed:15933009, PubMed:22453123). DmaW catalyzes the first step of ergot alkaloid biosynthesis by condensing dimethylallyl diphosphate (DMAP) and tryptophan to form 4-dimethylallyl-L-tryptophan (PubMed:15870460). The second step is catalyzed by the methyltransferase easF that methylates 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By similarity). The catalase easC and the FAD-dependent oxidoreductase easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is further oxidized by EasD in the presence of NAD(+), resulting in the formation of chanoclavine-I aldehyde (PubMed:20039019, PubMed:20526482, PubMed:21409592). EasA reduces chanoclavine-I aldehyde to dihydrochanoclavine-I aldehyde that spontaneously dehydrates to form 6,8-dimethyl-6,7-didehydroergoline (PubMed:20526482). EasG then catalyzes the reduction of 6,8-dimethyl-6,7-didehydroergoline to form festuclavine (PubMed:20526482). Hydrolysis of festuclavine by easM then leads to the formation of fumigaclavine B which is in turn acetylated by easN to fumigaclavine A (PubMed:26972831). Finally, easL catalyzes the conversion of fumigaclavine A into fumigaclavine C by attaching a dimethylallyl moiety to C-2 of the indole nucleus (PubMed:19672909).[UniProtKB:B6D5I7]<ref>PMID:15870460</ref> <ref>PMID:19672909</ref> <ref>PMID:20039019</ref> <ref>PMID:20526482</ref> <ref>PMID:21409592</ref> <ref>PMID:21898587</ref> <ref>PMID:22453123</ref> <ref>PMID:26972831</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aspfu]] | + | [[Category: Aspergillus fumigatus Af293]] |
| - | [[Category: Chanoclavine-I aldehyde reductase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lamb, A L]] | + | [[Category: Lamb AL]] |
| - | [[Category: Alpha/beta barrel]]
| + | |
| - | [[Category: Ergot alkaloid]]
| + | |
| - | [[Category: Old Yellow Enzyme]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Reductase]]
| + | |
| Structural highlights
Function
EASA_ASPFU Aldehyde reductase; part of the gene cluster that mediates the biosynthesis of fumiclavanine C, a fungal ergot alkaloid (PubMed:15933009, PubMed:22453123). DmaW catalyzes the first step of ergot alkaloid biosynthesis by condensing dimethylallyl diphosphate (DMAP) and tryptophan to form 4-dimethylallyl-L-tryptophan (PubMed:15870460). The second step is catalyzed by the methyltransferase easF that methylates 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By similarity). The catalase easC and the FAD-dependent oxidoreductase easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is further oxidized by EasD in the presence of NAD(+), resulting in the formation of chanoclavine-I aldehyde (PubMed:20039019, PubMed:20526482, PubMed:21409592). EasA reduces chanoclavine-I aldehyde to dihydrochanoclavine-I aldehyde that spontaneously dehydrates to form 6,8-dimethyl-6,7-didehydroergoline (PubMed:20526482). EasG then catalyzes the reduction of 6,8-dimethyl-6,7-didehydroergoline to form festuclavine (PubMed:20526482). Hydrolysis of festuclavine by easM then leads to the formation of fumigaclavine B which is in turn acetylated by easN to fumigaclavine A (PubMed:26972831). Finally, easL catalyzes the conversion of fumigaclavine A into fumigaclavine C by attaching a dimethylallyl moiety to C-2 of the indole nucleus (PubMed:19672909).[UniProtKB:B6D5I7][1] [2] [3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
The Aspergillus fumigatus old yellow enzyme (OYE) EasA reduces chanoclavine-I aldehyde to dihydrochanoclavine aldehyde and works in conjunction with festuclavine synthase at the branchpoint for ergot alkaloid pathways. The crystal structure of the FMN-loaded EasA was determined to 1.8 A resolution. The active-site amino acids of OYE are conserved, supporting a similar mechanism for reduction of the alpha/beta-unsaturated aldehyde. The C-terminal tail of one monomer packs into the active site of a monomer in the next asymmetric unit, which is most likely to be a crystallization artifact and not a mechanism of self-regulation.
Structure of an Aspergillus fumigatus old yellow enzyme (EasA) involved in ergot alkaloid biosynthesis.,Chilton AS, Ellis AL, Lamb AL Acta Crystallogr F Struct Biol Commun. 2014 Oct 1;70(Pt 10):1328-32. doi:, 10.1107/S2053230X14018962. Epub 2014 Sep 25. PMID:25286934[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Unsöld IA, Li SM. Overproduction, purification and characterization of FgaPT2, a dimethylallyltryptophan synthase from Aspergillus fumigatus. Microbiology (Reading). 2005 May;151(Pt 5):1499-1505. PMID:15870460 doi:10.1099/mic.0.27759-0
- ↑ Liu X, Wang L, Steffan N, Yin WB, Li SM. Ergot alkaloid biosynthesis in Aspergillus fumigatus: FgaAT catalyses the acetylation of fumigaclavine B. Chembiochem. 2009 Sep 21;10(14):2325-8. PMID:19672909 doi:10.1002/cbic.200900395
- ↑ Wallwey C, Matuschek M, Li SM. Ergot alkaloid biosynthesis in Aspergillus fumigatus: conversion of chanoclavine-I to chanoclavine-I aldehyde catalyzed by a short-chain alcohol dehydrogenase FgaDH. Arch Microbiol. 2010 Feb;192(2):127-34. PMID:20039019 doi:10.1007/s00203-009-0536-1
- ↑ Wallwey C, Matuschek M, Xie XL, Li SM. Ergot alkaloid biosynthesis in Aspergillus fumigatus: Conversion of chanoclavine-I aldehyde to festuclavine by the festuclavine synthase FgaFS in the presence of the old yellow enzyme FgaOx3. Org Biomol Chem. 2010 Aug 7;8(15):3500-8. PMID:20526482 doi:10.1039/c003823g
- ↑ Goetz KE, Coyle CM, Cheng JZ, O'Connor SE, Panaccione DG. Ergot cluster-encoded catalase is required for synthesis of chanoclavine-I in Aspergillus fumigatus. Curr Genet. 2011 Jun;57(3):201-11. doi: 10.1007/s00294-011-0336-4. Epub 2011 Mar , 17. PMID:21409592 doi:http://dx.doi.org/10.1007/s00294-011-0336-4
- ↑ Xie X, Wallwey C, Matuschek M, Steinbach K, Li SM. Formyl migration product of chanoclavine-I aldehyde in the presence of the old yellow enzyme FgaOx3 from Aspergillus fumigatus: a NMR structure elucidation. Magn Reson Chem. 2011 Oct;49(10):678-81. PMID:21898587 doi:10.1002/mrc.2796
- ↑ Robinson SL, Panaccione DG. Chemotypic and genotypic diversity in the ergot alkaloid pathway of Aspergillus fumigatus. Mycologia. 2012 Jul-Aug;104(4):804-12. PMID:22453123 doi:10.3852/11-310
- ↑ Bilovol Y, Panaccione DG. Functional analysis of the gene controlling hydroxylation of festuclavine in the ergot alkaloid pathway of Neosartorya fumigata. Curr Genet. 2016 Nov;62(4):853-860. PMID:26972831 doi:10.1007/s00294-016-0591-5
- ↑ Chilton AS, Ellis AL, Lamb AL. Structure of an Aspergillus fumigatus old yellow enzyme (EasA) involved in ergot alkaloid biosynthesis. Acta Crystallogr F Struct Biol Commun. 2014 Oct 1;70(Pt 10):1328-32. doi:, 10.1107/S2053230X14018962. Epub 2014 Sep 25. PMID:25286934 doi:http://dx.doi.org/10.1107/S2053230X14018962
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