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PDBsum entry 2oa6

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
2oa6
Jmol
Contents
Protein chains
295 a.a. *
Ligands
BME ×4
POP
GOL
Metals
_MG ×3
Waters ×236
* Residue conservation analysis
PDB id:
2oa6
Name: Lyase
Title: Aristolochene synthase from aspergillus terreus complexed wi pyrophosphate
Structure: Aristolochene synthase. Chain: a, b, c, d. Engineered: yes
Source: Aspergillus terreus. Organism_taxid: 33178. Gene: ari1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.15Å     R-factor:   0.229     R-free:   0.273
Authors: E.Y.Shishova,L.Di Costanzo,D.E.Cane,D.W.Christianson
Key ref: E.Y.Shishova et al. (2007). X-ray crystal structure of aristolochene synthase from Aspergillus terreus and evolution of templates for the cyclization of farnesyl diphosphate. Biochemistry, 46, 1941-1951. PubMed id: 17261032
Date:
15-Dec-06     Release date:   30-Jan-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9UR08  (Q9UR08_ASPTE) -  Aristolochene synthase
Seq:
Struc:
320 a.a.
295 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.3.9  - Aristolochene synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Germacrene derived sesquiterpenoid biosynthesis
      Reaction: (2E,6E)-farnesyl diphosphate = aristolochene + diphosphate
(2E,6E)-farnesyl diphosphate
= aristolochene
+ diphosphate
      Cofactor: Mg(2+); Mn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     lyase activity     5 terms  

 

 
    reference    
 
 
Biochemistry 46:1941-1951 (2007)
PubMed id: 17261032  
 
 
X-ray crystal structure of aristolochene synthase from Aspergillus terreus and evolution of templates for the cyclization of farnesyl diphosphate.
E.Y.Shishova, L.Di Costanzo, D.E.Cane, D.W.Christianson.
 
  ABSTRACT  
 
Aristolochene synthase from Aspergillus terreus catalyzes the cyclization of the universal sesquiterpene precursor, farnesyl diphosphate, to form the bicyclic hydrocarbon aristolochene. The 2.2 A resolution X-ray crystal structure of aristolochene synthase reveals a tetrameric quaternary structure in which each subunit adopts the alpha-helical class I terpene synthase fold with the active site in the "open", solvent-exposed conformation. Intriguingly, the 2.15 A resolution crystal structure of the complex with Mg2+3-pyrophosphate reveals ligand binding only to tetramer subunit D, which is stabilized in the "closed" conformation required for catalysis. Tetramer assembly may hinder conformational changes required for the transition from the inactive open conformation to the active closed conformation, thereby accounting for the attenuation of catalytic activity with an increase in enzyme concentration. In both conformations, but especially in the closed conformation, the active site contour is highly complementary in shape to that of aristolochene, and a catalytic function is proposed for the pyrophosphate anion based on its orientation with regard to the presumed binding mode of aristolochene. A similar active site contour is conserved in aristolochene synthase from Penicillium roqueforti despite the substantial divergent evolution of these two enzymes, while strikingly different active site contours are found in the sesquiterpene cyclases 5-epi-aristolochene synthase and trichodiene synthase. Thus, the terpenoid cyclase active site plays a critical role as a template in binding the flexible polyisoprenoid substrate in the proper conformation for catalysis. Across the greater family of terpenoid cyclases, this template is highly evolvable within a conserved alpha-helical fold for the synthesis of terpene natural products of diverse structure and stereochemistry.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21148562 B.Engels, U.Heinig, T.Grothe, M.Stadler, and S.Jennewein (2011).
Cloning and Characterization of an Armillaria gallica cDNA Encoding Protoilludene Synthase, Which Catalyzes the First Committed Step in the Synthesis of Antimicrobial Melleolides.
  J Biol Chem, 286, 6871-6878.  
21305070 K.Zhou, and R.J.Peters (2011).
Electrostatic effects on (di)terpene synthase product outcome.
  Chem Commun (Camb), 47, 4074-4080.  
20419721 F.Lopez-Gallego, S.A.Agger, D.Abate-Pella, M.D.Distefano, and C.Schmidt-Dannert (2010).
Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers.
  Chembiochem, 11, 1093-1106.  
20131801 J.A.Aaron, X.Lin, D.E.Cane, and D.W.Christianson (2010).
Structure of epi-isozizaene synthase from Streptomyces coelicolor A3(2), a platform for new terpenoid cyclization templates.
  Biochemistry, 49, 1787-1797.
PDB codes: 3kb9 3kbk 3lg5 3lgk
  20175559 J.P.Noel, N.Dellas, J.A.Faraldos, M.Zhao, B.A.Hess, L.Smentek, R.M.Coates, and P.E.O'Maille (2010).
Structural elucidation of cisoid and transoid cyclization pathways of a sesquiterpene synthase using 2-fluorofarnesyl diphosphates.
  ACS Chem Biol, 5, 377-392.
PDB codes: 3lz9 3m00 3m01 3m02
20725661 Y.J.Hong, and D.J.Tantillo (2010).
Quantum chemical dissection of the classic terpinyl/pinyl/bornyl/camphyl cation conundrum-the role of pyrophosphate in manipulating pathways to monoterpenes.
  Org Biomol Chem, 8, 4589-4600.  
19858213 B.Zhao, L.Lei, D.G.Vassylyev, X.Lin, D.E.Cane, S.L.Kelly, H.Yuan, D.C.Lamb, and M.R.Waterman (2009).
Crystal structure of albaflavenone monooxygenase containing a moonlighting terpene synthase active site.
  J Biol Chem, 284, 36711-36719.
PDB codes: 3dbg 3el3
19489610 H.A.Gennadios, V.Gonzalez, L.Di Costanzo, A.Li, F.Yu, D.J.Miller, R.K.Allemann, and D.W.Christianson (2009).
Crystal structure of (+)-delta-cadinene synthase from Gossypium arboreum and evolutionary divergence of metal binding motifs for catalysis.
  Biochemistry, 48, 6175-6183.
PDB codes: 3g4d 3g4f
19400802 S.Agger, F.Lopez-Gallego, and C.Schmidt-Dannert (2009).
Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus.
  Mol Microbiol, 72, 1181-1195.  
19181671 S.Green, C.J.Squire, N.J.Nieuwenhuizen, E.N.Baker, and W.Laing (2009).
Defining the potassium binding region in an apple terpene synthase.
  J Biol Chem, 284, 8661-8669.  
19635410 S.Y.Kim, P.Zhao, M.Igarashi, R.Sawa, T.Tomita, M.Nishiyama, and T.Kuzuyama (2009).
Cloning and heterologous expression of the cyclooctatin biosynthetic gene cluster afford a diterpene cyclase and two p450 hydroxylases.
  Chem Biol, 16, 736-743.  
19030608 B.M.Fraga (2008).
Natural sesquiterpenoids.
  Nat Prod Rep, 25, 1180-1209.  
18563268 D.J.Miller, J.Gao, D.G.Truhlar, N.J.Young, V.Gonzalez, and R.K.Allemann (2008).
Stereochemistry of eudesmane cation formation during catalysis by aristolochene synthase from Penicillium roqueforti.
  Org Biomol Chem, 6, 2346-2354.  
18651187 D.Lubertozzi, and J.D.Keasling (2008).
Expression of a synthetic Artemesia annua amorphadiene synthase in Aspergillus nidulans yields altered product distribution.
  J Ind Microbiol Biotechnol, 35, 1191-1198.  
18249199 D.W.Christianson (2008).
Unearthing the roots of the terpenome.
  Curr Opin Chem Biol, 12, 141-150.  
18385128 E.Y.Shishova, F.Yu, D.J.Miller, J.A.Faraldos, Y.Zhao, R.M.Coates, R.K.Allemann, D.E.Cane, and D.W.Christianson (2008).
X-ray crystallographic studies of substrate binding to aristolochene synthase suggest a metal ion binding sequence for catalysis.
  J Biol Chem, 283, 15431-15439.
PDB codes: 3bnx 3bny 3cke
18518825 L.L.Lairson, B.Henrissat, G.J.Davies, and S.G.Withers (2008).
Glycosyltransferases: structures, functions, and mechanisms.
  Annu Rev Biochem, 77, 521-555.  
17996718 L.S.Vedula, J.Jiang, T.Zakharian, D.E.Cane, and D.W.Christianson (2008).
Structural and mechanistic analysis of trichodiene synthase using site-directed mutagenesis: probing the catalytic function of tyrosine-295 and the asparagine-225/serine-229/glutamate-233-Mg2+B motif.
  Arch Biochem Biophys, 469, 184-194.
PDB codes: 2ps4 2ps5 2ps6 2ps7 2ps8
18658271 S.A.Agger, F.Lopez-Gallego, T.R.Hoye, and C.Schmidt-Dannert (2008).
Identification of sesquiterpene synthases from Nostoc punctiforme PCC 73102 and Nostoc sp. strain PCC 7120.
  J Bacteriol, 190, 6084-6096.  
18524777 T.G.Köllner, C.Schnee, S.Li, A.Svatos, B.Schneider, J.Gershenzon, and J.Degenhardt (2008).
Protonation of a neutral (S)-beta-bisabolene intermediate is involved in (S)-beta-macrocarpene formation by the maize sesquiterpene synthases TPS6 and TPS11.
  J Biol Chem, 283, 20779-20788.  
17683054 D.J.Miller, F.Yu, and R.K.Allemann (2007).
Aristolochene synthase-catalyzed cyclization of 2-fluorofarnesyl-diphosphate to 2-fluorogermacrene A.
  Chembiochem, 8, 1819-1825.  
17925960 F.Yu, D.J.Miller, and R.K.Allemann (2007).
Probing the reaction mechanism of aristolochene synthase with 12,13-difluorofarnesyl diphosphate.
  Chem Commun (Camb), (), 4155-4157.  
17918834 R.K.Allemann, N.J.Young, S.Ma, D.G.Truhlar, and J.Gao (2007).
Synthetic efficiency in enzyme mechanisms involving carbocations: aristolochene synthase.
  J Am Chem Soc, 129, 13008-13013.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.