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PDBsum entry 1f1k
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Lyase PDB id
1f1k

 

 

 

 

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Contents
Protein chain
290 a.a.
Ligands
ION
Theoretical model
PDB id:
1f1k
Name: Lyase
Title: Theoretical model of the enzyme-product complex of aristolochene synthase
Structure: Aristolochene synthase. Chain: a. Engineered: yes
Source: Penicillium roqueforti. Fungi. Expressed in: escherichia coli.
Authors: J.M.Caruthers,I.Kang,M.J.Rynkiewicz,D.E.Cane, D.W.Christianson
Key ref:
J.M.Caruthers et al. (2000). Crystal structure determination of aristolochene synthase from the blue cheese mold, Penicillium roqueforti. J Biol Chem, 275, 25533-25539. PubMed id: 10825154 DOI: 10.1074/jbc.M000433200
Date:
19-May-00     Release date:   24-Aug-00    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q03471  (ARIS_PENRO) -  Aristolochene synthase
Seq:
Struc: 		342 a.a.
290 a.a.
Key:    PfamA domain  Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.4.1.99.7  - Transferred entry: 4.2.3.9.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1074/jbc.M000433200 J Biol Chem 275:25533-25539 (2000)
PubMed id: 10825154  
 
 
Crystal structure determination of aristolochene synthase from the blue cheese mold, Penicillium roqueforti.
J.M.Caruthers, I.Kang, M.J.Rynkiewicz, D.E.Cane, D.W.Christianson.
 
  ABSTRACT  
 
The 2.5-A resolution crystal structure of recombinant aristolochene synthase from the blue cheese mold, Penicillium roqueforti, is the first of a fungal terpenoid cyclase. The structure of the enzyme reveals active site features that participate in the cyclization of the universal sesquiterpene cyclase substrate, farnesyl diphosphate, to form the bicyclic hydrocarbon aristolochene. Metal-triggered carbocation formation initiates the cyclization cascade, which proceeds through multiple complex intermediates to yield one exclusive structural and stereochemical isomer of aristolochene. Structural homology of this fungal cyclase with plant and bacterial terpenoid cyclases, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of terpene biosynthesis.
 
  Selected figure(s)  
 
Figure 4.
Fig. 4. Evolution of sesquiterpene biosynthetic pathways. Structural comparison of terpenoid synthases reveals that each enzyme in the biosynthetic pathway is a variation of the "terpenoid synthase fold," despite insignificant amino acid sequence identities. This structural comparison indicates evolutionary divergence of animal, plant, bacterial, and fungal cyclases from a common primordial ancestor. 		Figure 6.
Fig. 6. Structure-based mechanism of P. roqueforti aristolochene synthase. Models of the enzyme complexed with substrate, intermediates, and product are shown; salient mechanistic details are outlined in the text and appear schematically in Fig. 5. Briefly, farnesyl diphosphate binds in the unique productive conformation prior to the departure of the diphosphate leaving group (A). The initial cyclization yields the germacrene A intermediate through formation of the C-1-C-10 bond (B) (the diphosphate leaving group is not shown for clarity). Protonation of C-6 by Tyr-92 accompanied by C-2-C-7 bond formation closes the 10-membered ring of germacrene A to form the bicyclic eudesmane cation intermediate (C). A 1,2-hydride transfer, accompanied by a C-14 methyl migration and the elimination of H 8, yield aristolochene (D). Figure prepared with AVS (44).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 25533-25539) copyright 2000.  
  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.  
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
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.  
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.  
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.  
17912381 D.J.Miller, F.Yu, N.J.Young, and R.K.Allemann (2007).
Competitive inhibition of aristolochene synthase by phenyl-substituted farnesyl diphosphates: evidence of active site plasticity.
  Org Biomol Chem, 5, 3287-3298.  
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.  
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.  
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.  
17653361 S.Schulz, and J.S.Dickschat (2007).
Bacterial volatiles: the smell of small organisms.
  Nat Prod Rep, 24, 814-842.  
17115212 S.T.Withers, and J.D.Keasling (2007).
Biosynthesis and engineering of isoprenoid small molecules.
  Appl Microbiol Biotechnol, 73, 980-990.  
17353138 Y.Yoshikuni, and J.D.Keasling (2007).
Pathway engineering by designed divergent evolution.
  Curr Opin Chem Biol, 11, 233-239.  
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.  
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.  
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
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
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.  
11698643 M.J.Rynkiewicz, D.E.Cane, and D.W.Christianson (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.
PDB codes: 1jfa 1jfg
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.

 

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