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[[Image:2aet.gif|left|200px]]
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{{STRUCTURE_2aet|  PDB=2aet  |  SCENE=  }}
'''R304K trichodiene synthase: Complex with Mg, pyrophosphate, and (4S)-7-azabisabolene'''


==R304K trichodiene synthase: Complex with Mg, pyrophosphate, and (4S)-7-azabisabolene==
<StructureSection load='2aet' size='340' side='right'caption='[[2aet]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2aet]] is a 2 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=2AET OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AET 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]] 2.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</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=2aet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aet OCA], [https://pdbe.org/2aet PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aet RCSB], [https://www.ebi.ac.uk/pdbsum/2aet PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aet ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRI5_FUSSP TRI5_FUSSP] TS is a member of the terpene cyclase group of enzymes. It catalyzes the isomerization and cyclization of farnesyl pyro-phosphate to form trichodiene, the first cyclic intermediate in the biosynthetic pathway for trichothecenes. It serves to branch trichothecene biosynthesis from the isoprenoid pathway.
== 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/ae/2aet_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=2aet ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The X-ray crystal structures of R304K trichodiene synthase and its complexes with inorganic pyrophosphate (PP(i)) and aza analogues of the bisabolyl carbocation intermediate are reported. The R304K substitution does not cause large changes in the overall structure in comparison with the wild-type enzyme. The complexes with (R)- and (S)-azabisabolenes and PP(i) bind three Mg2+ ions, and each undergoes a diphosphate-triggered conformational change that caps the active site cavity. This conformational change is only slightly attenuated compared to that of the wild-type enzyme complexed with Mg2+(3)-PP(i), in which R304 donates hydrogen bonds to PP(i) and D101. In R304K trichodiene synthase, K304 does not engage in any hydrogen bond interactions in the unliganded state and it donates a hydrogen bond to only PP(i) in the complex with (R)-azabisabolene; K304 makes no hydrogen bond contacts in its complex with PP(i) and (S)-azabisabolene. Thus, although the R304-D101 hydrogen bond interaction stabilizes diphosphate-triggered active site closure, it is not required for Mg2+(3)-PP(i) binding. Nevertheless, since R304K trichodiene synthase generates aberrant cyclic terpenoids with a 5000-fold reduction in kcat/KM, it is clear that a properly formed R304-D101 hydrogen bond is required in the enzyme-substrate complex to stabilize the proper active site contour, which in turn facilitates cyclization of farnesyl diphosphate for the exclusive formation of trichodiene. Structural analysis of the R304K mutant and comparison with the monoterpene cyclase (+)-bornyl diphosphate synthase suggest that the significant loss in activity results from compromised activation of the PP(i) leaving group.


==Overview==
Role of arginine-304 in the diphosphate-triggered active site closure mechanism of trichodiene synthase.,Vedula LS, Cane DE, Christianson DW Biochemistry. 2005 Sep 27;44(38):12719-27. PMID:16171386<ref>PMID:16171386</ref>
The X-ray crystal structures of R304K trichodiene synthase and its complexes with inorganic pyrophosphate (PP(i)) and aza analogues of the bisabolyl carbocation intermediate are reported. The R304K substitution does not cause large changes in the overall structure in comparison with the wild-type enzyme. The complexes with (R)- and (S)-azabisabolenes and PP(i) bind three Mg2+ ions, and each undergoes a diphosphate-triggered conformational change that caps the active site cavity. This conformational change is only slightly attenuated compared to that of the wild-type enzyme complexed with Mg2+(3)-PP(i), in which R304 donates hydrogen bonds to PP(i) and D101. In R304K trichodiene synthase, K304 does not engage in any hydrogen bond interactions in the unliganded state and it donates a hydrogen bond to only PP(i) in the complex with (R)-azabisabolene; K304 makes no hydrogen bond contacts in its complex with PP(i) and (S)-azabisabolene. Thus, although the R304-D101 hydrogen bond interaction stabilizes diphosphate-triggered active site closure, it is not required for Mg2+(3)-PP(i) binding. Nevertheless, since R304K trichodiene synthase generates aberrant cyclic terpenoids with a 5000-fold reduction in kcat/KM, it is clear that a properly formed R304-D101 hydrogen bond is required in the enzyme-substrate complex to stabilize the proper active site contour, which in turn facilitates cyclization of farnesyl diphosphate for the exclusive formation of trichodiene. Structural analysis of the R304K mutant and comparison with the monoterpene cyclase (+)-bornyl diphosphate synthase suggest that the significant loss in activity results from compromised activation of the PP(i) leaving group.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2AET is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Fusarium_sporotrichioides Fusarium sporotrichioides]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AET OCA].
</div>
<div class="pdbe-citations 2aet" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Role of arginine-304 in the diphosphate-triggered active site closure mechanism of trichodiene synthase., Vedula LS, Cane DE, Christianson DW, Biochemistry. 2005 Sep 27;44(38):12719-27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16171386 16171386]
*[[Trichodiene synthase|Trichodiene synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Fusarium sporotrichioides]]
[[Category: Fusarium sporotrichioides]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Trichodiene synthase]]
[[Category: Cane DE]]
[[Category: Cane, D E.]]
[[Category: Christianson DW]]
[[Category: Christianson, D W.]]
[[Category: Vedula LS]]
[[Category: Vedula, L S.]]
[[Category: Pyrophosphate]]
[[Category: Site-directed mutagenesis]]
[[Category: Terpenoid synthase fold]]
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Retrieved from "https://proteopedia.org/2aet"