PDBsum entry 1n20

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protein ligands metals Protein-protein interface(s) links
Isomerase PDB id
Protein chains
532 a.a. *
3AG ×2
_MG ×6
Waters ×269
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: (+)-Bornyl diphosphate synthase: complex with mg and 3-aza- 2,3-dihydrogeranyl diphosphate
Structure: (+)-Bornyl diphosphate synthase. Chain: a, b. Fragment: residue 50-598. Engineered: yes
Source: Salvia officinalis. Garden sage. Organism_taxid: 38868. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.30Å     R-factor:   0.205     R-free:   0.228
Authors: D.A.Whittington,M.L.Wise,M.Urbansky,R.M.Coates,R.B.Croteau, D.W.Christianson
Key ref:
D.A.Whittington et al. (2002). Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase. Proc Natl Acad Sci U S A, 99, 15375-15380. PubMed id: 12432096 DOI: 10.1073/pnas.232591099
21-Oct-02     Release date:   27-Nov-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O81192  (BPPS_SALOF) -  (+)-bornyl diphosphate synthase, chloroplastic
598 a.a.
532 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.  - (+)-camphene synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Geranyl diphosphate = +-camphene + diphosphate
Geranyl diphosphate
Bound ligand (Het Group name = 3AG)
matches with 40.74% similarity
= (+)-camphene
+ diphosphate
   Enzyme class 3: E.C.  - (+)-alpha-pinene synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Geranyl diphosphate = +-alpha-pinene + diphosphate
Geranyl diphosphate
= (+)-alpha-pinene
+ diphosphate
   Enzyme class 4: E.C.  - (+)-bornyl diphosphate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: Geranyl diphosphate = +-bornyl diphosphate
Geranyl diphosphate
= (+)-bornyl diphosphate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     plastid   2 terms 
  Biological process     metabolic process   2 terms 
  Biochemical function     lyase activity     6 terms  


DOI no: 10.1073/pnas.232591099 Proc Natl Acad Sci U S A 99:15375-15380 (2002)
PubMed id: 12432096  
Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase.
D.A.Whittington, M.L.Wise, M.Urbansky, R.M.Coates, R.B.Croteau, D.W.Christianson.
The x-ray crystal structure of dimeric (+)-bornyl diphosphate synthase, a metal-requiring monoterpene cyclase from Salvia officinalis, is reported at 2.0-A resolution. Each monomer contains two alpha-helical domains: the C-terminal domain catalyzes the cyclization of geranyl diphosphate, orienting and stabilizing multiple reactive carbocation intermediates; the N-terminal domain has no clearly defined function, although its N terminus caps the active site in the C-terminal domain during catalysis. Structures of complexes with aza analogues of substrate and carbocation intermediates, as well as complexes with pyrophosphate and bornyl diphosphate, provide "snapshots" of the terpene cyclization cascade.
  Selected figure(s)  
Figure 2.
Fig 2. (A) Stereoplot of the native BPPS monomer; the viewer is looking into the active site in the C-terminal domain (blue); helical segments are designated by the convention used for farnesyl diphosphate synthase (11). The aspartate-rich motif is red, and the second metal-binding motif starting at D496 is orange. The N-terminal domain is green. Disordered segments (E50-A63, E228-I233, T500-D509, and G579-S583) are indicated by dotted lines. (B) Stereoplot of the BPPS monomer complexed with PP[i] (black); orientation is the same as in A. The diphosphate group of GPP similarly triggers conformational changes that order three polypeptide segments to cap the active site: most of the N terminus (I54-A63), the C-terminal portion of helix H and the H- 1 loop (T500-D509), and a portion of the J-K loop (G579-S583). (C) Structure of the BPPS dimer; the left-hand monomer is oriented 90° down from the orientation shown in A. The dimer interface is formed by the C terminus of helix A, and helices D1, D2, and E (1,167 Å2 surface area per monomer is excluded from solvent).
Figure 5.
Fig 5. GPP cyclization pathway in the active site of BPPS, represented by its solvent-accessible surface area. Note that water #110 comprises an integral part of the active site template. The modeling of GPP (A) is based on the binding conformation of inhibitor 1, which may not be a faithful representation of the native substrate. GPP can also bind in a more compact conformer that requires less rearrangement to form the (3R)-LPP (B and C).
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21443633 F.Chen, D.Tholl, J.Bohlmann, and E.Pichersky (2011).
The family of terpene synthases in plants: a mid-size family of genes for specialized metabolism that is highly diversified throughout the kingdom.
  Plant J, 66, 212-229.  
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
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
20602361 R.Cao, Y.Zhang, F.M.Mann, C.Huang, D.Mukkamala, M.P.Hudock, M.E.Mead, S.Prisic, K.Wang, F.Y.Lin, T.K.Chang, R.J.Peters, and E.Oldfield (2010).
Diterpene cyclases and the nature of the isoprene fold.
  Proteins, 78, 2417-2432.  
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.  
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.  
19217864 D.Long, and D.Yang (2009).
Buffer interference with protein dynamics: a case study on human liver fatty acid binding protein.
  Biophys J, 96, 1482-1488.  
19547916 F.Yu, and R.Utsumi (2009).
Diversity, regulation, and genetic manipulation of plant mono- and sesquiterpenoid biosynthesis.
  Cell Mol Life Sci, 66, 3043-3052.  
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.  
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.  
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
17440821 C.C.van Schie, M.A.Haring, and R.C.Schuurink (2007).
Tomato linalool synthase is induced in trichomes by jasmonic acid.
  Plant Mol Biol, 64, 251-263.  
17372193 D.C.Hyatt, B.Youn, Y.Zhao, B.Santhamma, R.M.Coates, R.B.Croteau, and C.Kang (2007).
Structure of limonene synthase, a simple model for terpenoid cyclase catalysis.
  Proc Natl Acad Sci U S A, 104, 5360-5365.
PDB codes: 2ong 2onh
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
17949678 F.Karp, Y.Zhao, B.Santhamma, B.Assink, R.M.Coates, and R.B.Croteau (2007).
Inhibition of monoterpene cyclases by inert analogues of geranyl diphosphate and linalyl diphosphate.
  Arch Biochem Biophys, 468, 140-146.  
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
17456599 M.Xu, P.R.Wilderman, and R.J.Peters (2007).
Following evolution's lead to a single residue switch for diterpene synthase product outcome.
  Proc Natl Acad Sci U S A, 104, 7397-7401.  
16684230 C.I.Keeling, and J.Bohlmann (2006).
Genes, enzymes and chemicals of terpenoid diversity in the constitutive and induced defence of conifers against insects and pathogens.
  New Phytol, 170, 657-675.  
16600670 D.Tholl (2006).
Terpene synthases and the regulation, diversity and biological roles of terpene metabolism.
  Curr Opin Plant Biol, 9, 297-304.  
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
16032349 T.Tokiwano, T.Endo, T.Tsukagoshi, H.Goto, E.Fukushi, and H.Oikawa (2005).
Proposed mechanism for diterpene synthases in the formation of phomactatriene and taxadiene.
  Org Biomol Chem, 3, 2713-2722.  
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
15602548 J.Clardy, and C.Walsh (2004).
Lessons from natural molecules.
  Nature, 432, 829-837.  
15255861 M.Xu, M.L.Hillwig, S.Prisic, R.M.Coates, and R.J.Peters (2004).
Functional identification of rice syn-copalyl diphosphate synthase and its role in initiating biosynthesis of diterpenoid phytoalexin/allelopathic natural products.
  Plant J, 39, 309-318.  
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.  
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.