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The | ==Structural and Functional Characterization of TRI3 Trichothecene 15-O-acetyltransferase from Fusarium sporotrichioides== | ||
<StructureSection load='3fp0' size='340' side='right'caption='[[3fp0]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3fp0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Fusarium_sporotrichioides Fusarium sporotrichioides]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FP0 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=FP0:(3ALPHA)-15-HYDROXY-12,13-EPOXYTRICHOTHEC-9-EN-3-YL+ACETATE'>FP0</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900032:surcrose+isoform'>PRD_900032</scene>, <scene name='pdbligand=Z9N:alpha-D-fructofuranose'>Z9N</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=3fp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fp0 OCA], [https://pdbe.org/3fp0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fp0 RCSB], [https://www.ebi.ac.uk/pdbsum/3fp0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fp0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRI3_FUSSP TRI3_FUSSP] 15-O-acetyltransferase; part of the core gene cluster that mediates the biosynthesis of trichothecenes, a very large family of chemically related bicyclic sesquiterpene compounds acting as mycotoxins, including T2-toxin (PubMed:8593041, PubMed:19319932). The biosynthesis of trichothecenes begins with the cyclization of farnesyl diphosphate to trichodiene and is catalyzed by the trichodiene synthase TRI5 (PubMed:3800398). Trichodiene undergoes a series of oxygenations catalyzed by the cytochrome P450 monooxygenase TRI4 (PubMed:7651333). TRI4 controls the addition of four oxygens at C-2, C-3, C-11, and the C-12, C-13-epoxide to form the intermediate isotrichotriol (PubMed:16917519). Isotrichotriol then undergoes a non-enzymatic isomerization and cyclization to form isotrichodermol (PubMed:2317042). During this process, the oxygen at the C-2 position becomes the pyran ring oxygen and the hydroxyl group at C-11 is lost (PubMed:2317042). More complex type A trichothecenes are built by modifying isotrichodermol through a series of paired hydroxylation and acetylation or acylation steps (PubMed:11352533). Isotrichodermol is converted to isotrichodermin by the acetyltransferase TRI101 (PubMed:10583973). TRI101 encodes a C-3 transacetylase that acts as a self-protection or resistance factor during biosynthesis and that the presence of a free C-3 hydroxyl group is a key component of Fusarium trichothecene phytotoxicity (PubMed:10583973). A second hydroxyl group is added to C-15 by the trichothecene C-15 hydroxylase TRI11, producing 15-decalonectrin, which is then acetylated by TRI3, producing calonectrin (PubMed:9435078, PubMed:8593041, PubMed:19319932). A third hydroxyl group is added at C-4 by the cytochrome P450 monooxygenase TRI13, converting calonectrin to 3,15-diacetoxyspirpenol, which is subsequently acetylated by the acetyltransferase TRI7 (PubMed:12135578, PubMed:11352533). A fourth hydroxyl group is added to C-8 by the cytochrome P450 monooxygenase TRI1, followed by the addition of an isovaleryl moiety by TRI16 (PubMed:12620849, PubMed:14532047). Finally, the acetyl group is removed from the C-3 position by the trichothecene C-3 esterase TRI8 to produce T-2 toxin (PubMed:12039755).<ref>PMID:10583973</ref> <ref>PMID:11352533</ref> <ref>PMID:12039755</ref> <ref>PMID:12135578</ref> <ref>PMID:12620849</ref> <ref>PMID:14532047</ref> <ref>PMID:16917519</ref> <ref>PMID:19319932</ref> <ref>PMID:2317042</ref> <ref>PMID:3800398</ref> <ref>PMID:7651333</ref> <ref>PMID:8593041</ref> <ref>PMID:9435078</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fp/3fp0_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fp0 ConSurf]. | |||
<div style="clear:both"></div> | |||
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== Publication Abstract from PubMed == | |||
Fusarium head blight is a devastating disease of cereal crops whose worldwide incidence is increasing and at present there is no satisfactory way of combating this pathogen or its associated toxins. There is a wide variety of trichothecene mycotoxins and they all contain a 12,13-epoxytrichothecene skeleton but differ in their substitutions. Indeed, there is considerable variation in the toxin profile across the numerous Fusarium species that has been ascribed to differences in the presence or absence of biosynthetic enzymes and their relative activity. This article addresses the source of differences in acetylation at the C15 position of the trichothecene molecule. Here, we present the in vitro structural and biochemical characterization of TRI3, a 15-O-trichothecene acetyltransferase isolated from F. sporotrichioides and the "in vivo" characterization of Deltatri3 mutants of deoxynivalenol (DON) producing F. graminearum strains. A kinetic analysis shows that TRI3 is an efficient enzyme with the native substrate, 15-decalonectrin, but is inactive with either DON or nivalenol. The structure of TRI3 complexed with 15-decalonectrin provides an explanation for this specificity and shows that Tri3 and Tri101 (3-O-trichothecene acetyltransferase) are evolutionarily related. The active site residues are conserved across all sequences for TRI3 orthologs, suggesting that differences in acetylation at C15 are not due to differences in Tri3. The tri3 deletion mutant shows that acetylation at C15 is required for DON biosynthesis even though DON lacks a C15 acetyl group. The enzyme(s) responsible for deacetylation at the 15 position of the trichothecene mycotoxins have not been identified. | |||
Structural and functional characterization of TRI3 trichothecene 15-O-acetyltransferase from Fusarium sporotrichioides.,Garvey GS, McCormick SP, Alexander NJ, Rayment I Protein Sci. 2009 Apr;18(4):747-61. PMID:19319932<ref>PMID:19319932</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3fp0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Fusarium sporotrichioides]] | |||
[[Category: Large Structures]] | |||
[[Category: Alexander NJ]] | |||
[[Category: Garvey GS]] | |||
[[Category: McCormick SP]] | |||
[[Category: Rayment I]] | |||