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| - | [[Image:3bnx.jpg|left|200px]] | |
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| - | {{Structure
| + | ==Crystal structure of Aristolochene synthase complexed with farnesyl diphosphate== |
| - | |PDB= 3bnx |SIZE=350|CAPTION= <scene name='initialview01'>3bnx</scene>, resolution 2.10Å
| + | <StructureSection load='3bnx' size='340' side='right'caption='[[3bnx]], [[Resolution|resolution]] 2.10Å' scene=''> |
| - | |SITE= <scene name='pdbsite=AC1:Mg+Binding+Site+For+Residue+D+701'>AC1</scene>, <scene name='pdbsite=AC2:Fpp+Binding+Site+For+Residue+A+400'>AC2</scene>, <scene name='pdbsite=AC3:Bme+Binding+Site+For+Residue+B+1271'>AC3</scene>, <scene name='pdbsite=AC4:Fpp+Binding+Site+For+Residue+B+401'>AC4</scene>, <scene name='pdbsite=AC5:Bme+Binding+Site+For+Residue+C+1270'>AC5</scene>, <scene name='pdbsite=AC6:Fpp+Binding+Site+For+Residue+C+402'>AC6</scene>, <scene name='pdbsite=AC7:Bme+Binding+Site+For+Residue+D+1274'>AC7</scene>, <scene name='pdbsite=AC8:Pop+Binding+Site+For+Residue+D+4294'>AC8</scene> and <scene name='pdbsite=AC9:Gol+Binding+Site+For+Residue+C+2647'>AC9</scene>
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene>
| + | <table><tr><td colspan='2'>[[3bnx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_terreus Aspergillus terreus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BNX FirstGlance]. <br> |
| - | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Aristolochene_synthase Aristolochene synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.9 4.2.3.9] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | |GENE= Ari1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=33178 Aspergillus terreus])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=FPP:FARNESYL+DIPHOSPHATE'>FPP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene></td></tr> |
| - | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd00687 Terpene_cyclase_nonplant_C1]</span>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bnx OCA], [https://pdbe.org/3bnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bnx RCSB], [https://www.ebi.ac.uk/pdbsum/3bnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bnx ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=[[2oa6|2OA6]], [[3bny|3BNY]]
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bnx OCA], [http://www.ebi.ac.uk/pdbsum/3bnx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bnx RCSB]</span>
| + | == Function == |
| - | }}
| + | [https://www.uniprot.org/uniprot/ARIS_ASPTE ARIS_ASPTE] Catalyzes the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic sesquiterpene aristolochene. Produces germacrene A as an enzyme-bound intermediate that is not released by the enzyme, but is further cyclized to produce aristolochene. Aristolochene is the likely parent compound for a number of sesquiterpenoid toxins produced by filamentous fungi.<ref>PMID:10775423</ref> <ref>PMID:15186158</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/bn/3bnx_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=3bnx ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The universal sesquiterpene precursor, farnesyl diphosphate (FPP), is cyclized in an Mg(2+)-dependent reaction catalyzed by the tetrameric aristolochene synthase from Aspergillus terreus to form the bicyclic hydrocarbon aristolochene and a pyrophosphate anion (PP(i)) coproduct. The 2.1-A resolution crystal structure determined from crystals soaked with FPP reveals the binding of intact FPP to monomers A-C, and the binding of PP(i) and Mg(2+)(B) to monomer D. The 1.89-A resolution structure of the complex with 2-fluorofarnesyl diphosphate (2F-FPP) reveals 2F-FPP binding to all subunits of the tetramer, with Mg(2+)(B)accompanying the binding of this analogue only in monomer D. All monomers adopt open activesite conformations in these complexes, but slight structural changes in monomers C and D of each complex reflect the very initial stages of a conformational transition to the closed state. Finally, the 2.4-A resolution structure of the complex with 12,13-difluorofarnesyl diphosphate (DF-FPP) reveals the binding of intact DF-FPP to monomers A-C in the open conformation and the binding of PP(i), Mg(2+)(B), and Mg(2+)(C) to monomer D in a predominantly closed conformation. Taken together, these structures provide 12 independent "snapshots" of substrate or product complexes that suggest a possible sequence for metal ion binding and conformational changes required for catalysis. |
| | | | |
| - | '''Crystal structure of Aristolochene synthase complexed with farnesyl diphosphate'''
| + | X-ray crystallographic studies of substrate binding to aristolochene synthase suggest a metal ion binding sequence for catalysis.,Shishova EY, Yu F, Miller DJ, Faraldos JA, Zhao Y, Coates RM, Allemann RK, Cane DE, Christianson DW J Biol Chem. 2008 May 30;283(22):15431-9. Epub 2008 Apr 2. PMID:18385128<ref>PMID:18385128</ref> |
| | | | |
| - | | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | ==About this Structure==
| + | </div> |
| - | 3BNX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Aspergillus_terreus Aspergillus terreus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BNX OCA].
| + | <div class="pdbe-citations 3bnx" style="background-color:#fffaf0;"></div> |
| - | [[Category: Aristolochene synthase]]
| + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Aspergillus terreus]] | | [[Category: Aspergillus terreus]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Christianson, D W.]] | + | [[Category: Christianson DW]] |
| - | [[Category: Shishova, E Y.]] | + | [[Category: Shishova EY]] |
| - | [[Category: cyclization]]
| + | |
| - | [[Category: farnesyl diphosphate]]
| + | |
| - | [[Category: isoprenoid]]
| + | |
| - | [[Category: lyase]]
| + | |
| - | [[Category: magnesium]]
| + | |
| - | [[Category: sesquiterpene cyclase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:27:43 2008''
| + | |
| Structural highlights
3bnx is a 4 chain structure with sequence from Aspergillus terreus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.1Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ARIS_ASPTE Catalyzes the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic sesquiterpene aristolochene. Produces germacrene A as an enzyme-bound intermediate that is not released by the enzyme, but is further cyclized to produce aristolochene. Aristolochene is the likely parent compound for a number of sesquiterpenoid toxins produced by filamentous fungi.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The universal sesquiterpene precursor, farnesyl diphosphate (FPP), is cyclized in an Mg(2+)-dependent reaction catalyzed by the tetrameric aristolochene synthase from Aspergillus terreus to form the bicyclic hydrocarbon aristolochene and a pyrophosphate anion (PP(i)) coproduct. The 2.1-A resolution crystal structure determined from crystals soaked with FPP reveals the binding of intact FPP to monomers A-C, and the binding of PP(i) and Mg(2+)(B) to monomer D. The 1.89-A resolution structure of the complex with 2-fluorofarnesyl diphosphate (2F-FPP) reveals 2F-FPP binding to all subunits of the tetramer, with Mg(2+)(B)accompanying the binding of this analogue only in monomer D. All monomers adopt open activesite conformations in these complexes, but slight structural changes in monomers C and D of each complex reflect the very initial stages of a conformational transition to the closed state. Finally, the 2.4-A resolution structure of the complex with 12,13-difluorofarnesyl diphosphate (DF-FPP) reveals the binding of intact DF-FPP to monomers A-C in the open conformation and the binding of PP(i), Mg(2+)(B), and Mg(2+)(C) to monomer D in a predominantly closed conformation. Taken together, these structures provide 12 independent "snapshots" of substrate or product complexes that suggest a possible sequence for metal ion binding and conformational changes required for catalysis.
X-ray crystallographic studies of substrate binding to aristolochene synthase suggest a metal ion binding sequence for catalysis.,Shishova EY, Yu F, Miller DJ, Faraldos JA, Zhao Y, Coates RM, Allemann RK, Cane DE, Christianson DW J Biol Chem. 2008 May 30;283(22):15431-9. Epub 2008 Apr 2. PMID:18385128[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cane DE, Kang I. Aristolochene synthase: purification, molecular cloning, high-level expression in Escherichia coli, and characterization of the Aspergillus terreus cyclase. Arch Biochem Biophys. 2000 Apr 15;376(2):354-64. PMID:10775423 doi:10.1006/abbi.2000.1734
- ↑ Felicetti B, Cane DE. Aristolochene synthase: mechanistic analysis of active site residues by site-directed mutagenesis. J Am Chem Soc. 2004 Jun 16;126(23):7212-21. PMID:15186158 doi:10.1021/ja0499593
- ↑ Shishova EY, Yu F, Miller DJ, Faraldos JA, Zhao Y, Coates RM, Allemann RK, Cane DE, Christianson DW. X-ray crystallographic studies of substrate binding to aristolochene synthase suggest a metal ion binding sequence for catalysis. J Biol Chem. 2008 May 30;283(22):15431-9. Epub 2008 Apr 2. PMID:18385128 doi:10.1074/jbc.M800659200
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