PDBsum entry 1jfg

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protein ligands metals links
Lyase PDB id
Protein chains
354 a.a. *
GOL ×3
_MG ×3
Waters ×292
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Trichodiene synthase from fusarium sporotrichioides complexe diphosphate
Structure: Trichodiene synthase. Chain: a, b. Synonym: sesquiterpene cyclase. Ts. Trichodiene synthase tr engineered: yes
Source: Fusarium sporotrichioides. Organism_taxid: 5514. Gene: tri5. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.50Å     R-factor:   0.217     R-free:   0.254
Authors: M.J.Rynkiewicz,D.E.Cane,D.W.Christianson
Key ref:
M.J.Rynkiewicz et al. (2001). Structure of trichodiene synthase from Fusarium sporotrichioides provides mechanistic inferences on the terpene cyclization cascade. Proc Natl Acad Sci U S A, 98, 13543-13548. PubMed id: 11698643 DOI: 10.1073/pnas.231313098
20-Jun-01     Release date:   30-Nov-01    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P13513  (TRI5_FUSSP) -  Trichodiene synthase
374 a.a.
354 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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

Bisabolene derived sesquiterpenoid biosynthesis
      Reaction: (2E,6E)-farnesyl diphosphate = trichodiene + diphosphate
(2E,6E)-farnesyl diphosphate
= trichodiene
Bound ligand (Het Group name = POP)
corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     sesquiterpenoid biosynthetic process   1 term 
  Biochemical function     lyase activity     2 terms  


DOI no: 10.1073/pnas.231313098 Proc Natl Acad Sci U S A 98:13543-13548 (2001)
PubMed id: 11698643  
Structure of trichodiene synthase from Fusarium sporotrichioides provides mechanistic inferences on the terpene cyclization cascade.
M.J.Rynkiewicz, D.E.Cane, D.W.Christianson.
The x-ray crystal structure of recombinant trichodiene synthase from Fusarium sporotrichioides has been determined to 2.5-A resolution, both unliganded and complexed with inorganic pyrophosphate. This reaction product coordinates to three Mg(2+) ions near the mouth of the active site cleft. A comparison of the liganded and unliganded structures reveals a ligand-induced conformational change that closes the mouth of the active site cleft. Binding of the substrate farnesyl diphosphate similarly may trigger this conformational change, which would facilitate catalysis by protecting reactive carbocationic intermediates in the cyclization cascade. Trichodiene synthase also shares significant structural similarity with other sesquiterpene synthases despite a lack of significant sequence identity. This similarity indicates divergence from a common ancestor early in the evolution of terpene biosynthesis.
  Selected figure(s)  
Figure 1.
Fig. 1. Cyclization of farnesyl diphosphate to trichodiene is the first committed step in the biosynthesis of nearly 100 different trichothecene toxins and antibiotics produced by as many as 10 genera of fungi, of which T-2 toxin in F. sporotrichioides is an example. OPP, diphosphate.
Figure 3.
Fig. 3. Structural similarity of terpene synthases. Regions of structural similarity (red) comprise the core terpenoid synthase fold. At the bottom are the rms deviation of C^ atoms and the number of structurally similar residues (in parentheses). The enzymes are trichodiene synthase (TS), farnesyl diphosphate synthase (FDPS, PDB code 1UBW), aristolochene synthase (AS, PDB code 1DI1), 5-epi-aristolochene synthase (EAS, PDB code 5EAT), pentalenene synthase (PS, PDB code 1PS1), and squalene synthase (SQS, PDB code 1EZF). OPP, diphosphate.
  Figures were selected by an automated process.  

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.  
21160477 M.Köksal, Y.Jin, R.M.Coates, R.Croteau, and D.W.Christianson (2011).
Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis.
  Nature, 469, 116-120.
PDB codes: 3p5p 3p5r
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
  20592812 N.J.Nieuwenhuizen, S.Green, and R.G.Atkinson (2010).
Floral sesquiterpenes and their synthesis in dioecious kiwifruit.
  Plant Signal Behav, 5, 61-63.  
20959422 Y.Kumeta, and M.Ito (2010).
Characterization of delta-guaiene synthases from cultured cells of Aquilaria, responsible for the formation of the sesquiterpenes in agarwood.
  Plant Physiol, 154, 1998-2007.  
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
19201430 K.Zhou, and R.J.Peters (2009).
Investigating the conservation pattern of a putative second terpene synthase divalent metal binding motif in plants.
  Phytochemistry, 70, 366-369.  
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.  
19763318 Y.J.Hong, and D.J.Tantillo (2009).
Modes of inactivation of trichodiene synthase by a cyclopropane-containing farnesyldiphosphate analog.
  Org Biomol Chem, 7, 4101-4109.  
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
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
18492804 M.Komatsu, M.Tsuda, S.Omura, H.Oikawa, and H.Ikeda (2008).
Identification and functional analysis of genes controlling biosynthesis of 2-methylisoborneol.
  Proc Natl Acad Sci U S A, 105, 7422-7427.  
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.  
17261032 E.Y.Shishova, L.Di Costanzo, D.E.Cane, and D.W.Christianson (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.
PDB codes: 2e4o 2oa6
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.  
17678871 L.S.Vedula, Y.Zhao, R.M.Coates, T.Koyama, D.E.Cane, and D.W.Christianson (2007).
Exploring biosynthetic diversity with trichodiene synthase.
  Arch Biochem Biophys, 466, 260-266.
PDB codes: 2q9y 2q9z
17115212 S.T.Withers, and J.D.Keasling (2007).
Biosynthesis and engineering of isoprenoid small molecules.
  Appl Microbiol Biotechnol, 73, 980-990.  
16785438 B.T.Greenhagen, P.E.O'Maille, J.P.Noel, and J.Chappell (2006).
Identifying and manipulating structural determinates linking catalytic specificities in terpene synthases.
  Proc Natl Acad Sci U S A, 103, 9826-9831.  
16804721 M.Mukherjee, B.A.Horwitz, P.D.Sherkhane, R.Hadar, and P.K.Mukherjee (2006).
A secondary metabolite biosynthesis cluster in Trichoderma virens: evidence from analysis of genes underexpressed in a mutant defective in morphogenesis and antibiotic production.
  Curr Genet, 50, 193-202.  
16555072 R.G.Kerr, A.C.Kohl, and T.A.Ferns (2006).
Elucidation of the biosynthetic origin of the anti-inflammatory pseudopterosins.
  J Ind Microbiol Biotechnol, 33, 532-538.  
16791319 S.Forcat, and R.K.Allemann (2006).
Stabilisation of transition states prior to and following eudesmane cation in aristolochene synthase.
  Org Biomol Chem, 4, 2563-2567.  
16495946 Y.Yoshikuni, T.E.Ferrin, and J.D.Keasling (2006).
Designed divergent evolution of enzyme function.
  Nature, 440, 1078-1082.  
16289312 F.Bouvier, A.Rahier, and B.Camara (2005).
Biogenesis, molecular regulation and function of plant isoprenoids.
  Prog Lipid Res, 44, 357-429.  
15789564 L.A.Wessjohann, E.Ruijter, D.Garcia-Rivera, and W.Brandt (2005).
What can a chemist learn from nature's macrocycles?--a brief, conceptual view.
  Mol Divers, 9, 171-186.  
16171386 L.S.Vedula, D.E.Cane, and D.W.Christianson (2005).
Role of arginine-304 in the diphosphate-triggered active site closure mechanism of trichodiene synthase.
  Biochemistry, 44, 12719-12727.
PDB codes: 2aek 2ael 2aet
16322742 N.P.Keller, G.Turner, and J.W.Bennett (2005).
Fungal secondary metabolism - from biochemistry to genomics.
  Nat Rev Microbiol, 3, 937-947.  
15113001 D.J.Reinert, G.Balliano, and G.E.Schulz (2004).
Conversion of squalene to the pentacarbocyclic hopene.
  Chem Biol, 11, 121-126.
PDB code: 1ump
12556563 D.E.Cane, and R.M.Watt (2003).
Expression and mechanistic analysis of a germacradienol synthase from Streptomyces coelicolor implicated in geosmin biosynthesis.
  Proc Natl Acad Sci U S A, 100, 1547-1551.  
12732318 J.Degenhardt, J.Gershenzon, I.T.Baldwin, and A.Kessler (2003).
Attracting friends to feast on foes: engineering terpene emission to make crop plants more attractive to herbivore enemies.
  Curr Opin Biotechnol, 14, 169-176.  
12432096 D.A.Whittington, M.L.Wise, M.Urbansky, R.M.Coates, R.B.Croteau, and D.W.Christianson (2002).
Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase.
  Proc Natl Acad Sci U S A, 99, 15375-15380.
PDB codes: 1n1b 1n1z 1n20 1n21 1n22 1n23 1n24
12084056 J.Lücker, M.K.El Tamer, W.Schwab, F.W.Verstappen, L.H.van der Plas, H.J.Bouwmeester, and H.A.Verhoeven (2002).
Monoterpene biosynthesis in lemon (Citrus limon). cDNA isolation and functional analysis of four monoterpene synthases.
  Eur J Biochem, 269, 3160-3171.  
11827517 M.J.Rynkiewicz, D.E.Cane, and D.W.Christianson (2002).
X-ray crystal structures of D100E trichodiene synthase and its pyrophosphate complex reveal the basis for terpene product diversity.
  Biochemistry, 41, 1732-1741.
PDB codes: 1kiy 1kiz
12135472 P.H.Liang, T.P.Ko, and A.H.Wang (2002).
Structure, mechanism and function of prenyltransferases.
  Eur J Biochem, 269, 3339-3354.  
11717417 B.Greenhagen, and J.Chappell (2001).
Molecular scaffolds for chemical wizardry: learning nature's rules for terpene cyclases.
  Proc Natl Acad Sci U S A, 98, 13479-13481.  
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.