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3cke

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Current revision

Crystal structure of aristolochene synthase in complex with 12,13-difluorofarnesyl diphosphate

Structural highlights

3cke 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 2.4Å
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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3cke"

@@ Line 3: / Line 3: @@
 <StructureSection load='3cke' size='340' side='right'caption='[[3cke]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3cke]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspte Aspte]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CKE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3cke]] 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=3CKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CKE FirstGlance]. <br>
-</td></tr><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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FDF:(2E,6E)-12-FLUORO-11-(FLUOROMETHYL)-3,7-DIMETHYLDODECA-2,6,10-TRIEN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>FDF</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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3bnx|3bnx]], [[3bny|3bny]]</div></td></tr>
+<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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FDF:(2E,6E)-12-FLUORO-11-(FLUOROMETHYL)-3,7-DIMETHYLDODECA-2,6,10-TRIEN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>FDF</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>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ari1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=33178 ASPTE])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Aristolochene_synthase Aristolochene synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.9 4.2.3.9] </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=3cke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cke OCA], [https://pdbe.org/3cke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cke RCSB], [https://www.ebi.ac.uk/pdbsum/3cke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cke ProSAT]</span></td></tr>
 </table>
 == 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>
+[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]]
@@ Line 35: / Line 33: @@
 __TOC__
 </StructureSection>
-[[Category: Aristolochene synthase]]
+[[Category: Aspergillus terreus]]
-[[Category: Aspte]]
 [[Category: Large Structures]]
-[[Category: Allemann, R K]]
+[[Category: Allemann RK]]
-[[Category: Cane, D E]]
+[[Category: Cane DE]]
-[[Category: Christianson, D W]]
+[[Category: Christianson DW]]
-[[Category: Coates, R M]]
+[[Category: Coates RM]]
-[[Category: Faraldos, J A]]
+[[Category: Faraldos JA]]
-[[Category: Miller, D J]]
+[[Category: Miller DJ]]
-[[Category: Shishova, E Y]]
+[[Category: Shishova EY]]
-[[Category: Yu, F]]
+[[Category: Yu F]]
-[[Category: Zhao, Y]]
+[[Category: Zhao Y]]
-[[Category: Catalysis]]
-[[Category: Conformational change]]
-[[Category: Lyase]]
-[[Category: Metal ion binding]]
-[[Category: Substrate binding]]

3cke

From Proteopedia

Current revision

Crystal structure of aristolochene synthase in complex with 12,13-difluorofarnesyl diphosphate

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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