PDBsum entry 1ps1

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Antibiotic biosynthesis PDB id
Protein chains
304 a.a. *
Waters ×66
* Residue conservation analysis
PDB id:
Name: Antibiotic biosynthesis
Title: Pentalenene synthase
Structure: Pentalenene synthase. Chain: a, b. Engineered: yes
Source: Streptomyces sp.. Organism_taxid: 74577. Strain: uc5319. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Monomer (from PDB file)
2.60Å     R-factor:   0.198     R-free:   0.273
Authors: C.A.Lesburg,D.W.Christianson
Key ref:
C.A.Lesburg et al. (1997). Crystal structure of pentalenene synthase: mechanistic insights on terpenoid cyclization reactions in biology. Science, 277, 1820-1824. PubMed id: 9295272 DOI: 10.1126/science.277.5333.1820
23-Mar-97     Release date:   25-Mar-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q55012  (PTLS_STRS3) -  Pentalenene synthase
337 a.a.
304 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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

Humulene derived sesquiterpenoid biosynthesis
      Reaction: (2E,6E)-farnesyl diphosphate = pentalenene + diphosphate
(2E,6E)-farnesyl diphosphate
= pentalenene
+ diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     antibiotic biosynthetic process   1 term 
  Biochemical function     lyase activity     5 terms  


DOI no: 10.1126/science.277.5333.1820 Science 277:1820-1824 (1997)
PubMed id: 9295272  
Crystal structure of pentalenene synthase: mechanistic insights on terpenoid cyclization reactions in biology.
C.A.Lesburg, G.Zhai, D.E.Cane, D.W.Christianson.
The crystal structure of pentalenene synthase at 2.6 angstrom resolution reveals critical active site features responsible for the cyclization of farnesyl diphosphate into the tricyclic hydrocarbon pentalenene. Metal-triggered substrate ionization initiates catalysis, and the alpha-barrel active site serves as a template to channel and stabilize the conformations of reactive carbocation intermediates through a complex cyclization cascade. The core active site structure of the enzyme may be preserved among the greater family of terpenoid synthases, possibly implying divergence from a common ancestral synthase to satisfy biological requirements for increasingly diverse natural products.
  Selected figure(s)  
Figure 5.
Fig. 5. Proposed mechanism for cyclization of farnesyl pyrophosphate to intermediates humulene and protoilludyl cation, with subsequent rearrangement into pentalenene (7, 14). The pyrophosphate^ leaving group is omitted for clarity; however, it may remain bound^ in the enzyme active site during the cyclization cascade and contribute^ to the electrostatic stabilization of carbocation intermediates.
Figure 6.
Fig. 6. (A) Farnesyl diphosphate must bind in the active site cleft with the correct conformation required for cyclization to pentalenene, with the C9-H oriented toward catalytic base His309 and the pyrophosphate moiety oriented toward the aspartate-rich segment through bridging Mg2+ (metal ions not shown for the sake of clarity). The trajectory of C-C bond formation leading to humulene synthesis in the initial cyclization step is indicated by a dashed line. (B) Pentalenene^ (as well as the preceding intermediates) is complementary in shape^ to the active site cavity. Comparison of substrate and product binding suggests that the active site is a template for correct conformation and stereochemistry in the cyclization cascade.
  The above figures are reprinted by permission from the AAAs: Science (1997, 277, 1820-1824) copyright 1997.  
  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
21276937 Y.Hu, W.K.Chou, R.Hopson, and D.E.Cane (2011).
Genome mining in Streptomyces clavuligerus: expression and biochemical characterization of two new cryptic sesquiterpene synthases.
  Chem Biol, 18, 32-37.  
  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
20229191 M.Fujisawa, H.Harada, H.Kenmoku, S.Mizutani, and N.Misawa (2010).
Cloning and characterization of a novel gene that encodes (S)-beta-bisabolene synthase from ginger, Zingiber officinale.
  Planta, 232, 121-130.  
20304090 P.D.Kiser, and K.Palczewski (2010).
Membrane-binding and enzymatic properties of RPE65.
  Prog Retin Eye Res, 29, 428-442.  
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.  
19636447 A.Koglin, and C.T.Walsh (2009).
Structural insights into nonribosomal peptide enzymatic assembly lines.
  Nat Prod Rep, 26, 987.  
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
19323569 C.D.Poulter, and C.D.Poulter (2009).
Bioorganic chemistry. A natural reunion of the physical and life sciences.
  J Org Chem, 74, 2631-2645.  
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
19485417 J.Jiang, C.N.Tetzlaff, S.Takamatsu, M.Iwatsuki, M.Komatsu, H.Ikeda, and D.E.Cane (2009).
Genome mining in Streptomyces avermitilis: A biochemical Baeyer-Villiger reaction and discovery of a new branch of the pentalenolactone family tree.
  Biochemistry, 48, 6431-6440.  
19447628 O.Henry, F.Lopez-Gallego, S.A.Agger, C.Schmidt-Dannert, S.Sen, D.Shintani, K.Cornish, and M.D.Distefano (2009).
A versatile photoactivatable probe designed to label the diphosphate binding site of farnesyl diphosphate utilizing enzymes.
  Bioorg Med Chem, 17, 4797-4805.  
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.  
18604568 C.Andreini, I.Bertini, G.Cavallaro, G.L.Holliday, and J.M.Thornton (2008).
Metal ions in biological catalysis: from enzyme databases to general principles.
  J Biol Inorg Chem, 13, 1205-1218.  
18249199 D.W.Christianson (2008).
Unearthing the roots of the terpenome.
  Curr Opin Chem Biol, 12, 141-150.  
18338424 L.Bräuer, W.Brandt, D.Schulze, S.Zakharova, and L.Wessjohann (2008).
A structural model of the membrane-bound aromatic prenyltransferase UbiA from E. coli.
  Chembiochem, 9, 982-992.  
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.  
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.  
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.  
16681390 C.N.Tetzlaff, Z.You, D.E.Cane, S.Takamatsu, S.Omura, and H.Ikeda (2006).
A gene cluster for biosynthesis of the sesquiterpenoid antibiotic pentalenolactone in Streptomyces avermitilis.
  Biochemistry, 45, 6179-6186.  
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.  
17191831 A.Goeke, D.Mertl, and G.Brunner (2004).
A novel approach to prezizaane sesquiterpenes.
  Chem Biodivers, 1, 1949-1956.  
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
14675427 E.M.Cho, A.Okada, H.Kenmoku, K.Otomo, T.Toyomasu, W.Mitsuhashi, T.Sassa, A.Yajima, G.Yabuta, K.Mori, H.Oikawa, H.Toshima, N.Shibuya, H.Nojiri, T.Omori, M.Nishiyama, and H.Yamane (2004).
Molecular cloning and characterization of a cDNA encoding ent-cassa-12,15-diene synthase, a putative diterpenoid phytoalexin biosynthetic enzyme, from suspension-cultured rice cells treated with a chitin elicitor.
  Plant J, 37, 1-8.  
12563033 B.Gust, G.L.Challis, K.Fowler, T.Kieser, and K.F.Chater (2003).
PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin.
  Proc Natl Acad Sci U S A, 100, 1541-1546.  
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
12112869 H.Ishibashi, K.Ishihara, and H.Yamamoto (2002).
Chiral proton donor reagents: tin tetrachloride--coordinated optically active binaphthol derivatives.
  Chem Rec, 2, 177-188.  
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.  
11805316 R.J.Peters, and R.B.Croteau (2002).
Abietadiene synthase catalysis: mutational analysis of a prenyl diphosphate ionization-initiated cyclization and rearrangement.
  Proc Natl Acad Sci U S A, 99, 580-584.  
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.  
11287651 M.Fujihashi, Y.W.Zhang, Y.Higuchi, X.Y.Li, T.Koyama, and K.Miki (2001).
Crystal structure of cis-prenyl chain elongating enzyme, undecaprenyl diphosphate synthase.
  Proc Natl Acad Sci U S A, 98, 4337-4342.
PDB code: 1f75
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
11287653 S.B.Rivera, B.D.Swedlund, G.J.King, R.N.Bell, C.E.Hussey, D.M.Shattuck-Eidens, W.M.Wrobel, G.D.Peiser, and C.D.Poulter (2001).
Chrysanthemyl diphosphate synthase: isolation of the gene and characterization of the recombinant non-head-to-tail monoterpene synthase from Chrysanthemum cinerariaefolium.
  Proc Natl Acad Sci U S A, 98, 4373-4378.  
  11404343 S.C.Trapp, and R.B.Croteau (2001).
Genomic organization of plant terpene synthases and molecular evolutionary implications.
  Genetics, 158, 811-832.  
11327834 T.Soderberg, and C.D.Poulter (2001).
Escherichia coli dimethylallyl diphosphate:tRNA dimethylallyltransferase: site-directed mutagenesis of highly conserved residues.
  Biochemistry, 40, 1734-1740.  
11285217 V.Durbecq, G.Sainz, Y.Oudjama, B.Clantin, C.Bompard-Gilles, C.Tricot, J.Caillet, V.Stalon, L.Droogmans, and V.Villeret (2001).
Crystal structure of isopentenyl diphosphate:dimethylallyl diphosphate isomerase.
  EMBO J, 20, 1530-1537.
PDB codes: 1hx3 1hzt
11054809 A.Bringmann, S.N.Skatchkov, F.Faude, V.Enzmann, and A.Reichenbach (2000).
Farnesol modulates membrane currents in human retinal glial cells.
  J Neurosci Res, 62, 396-402.  
10704208 C.Huang, K.E.Hightower, and C.A.Fierke (2000).
Mechanistic studies of rat protein farnesyltransferase indicate an associative transition state.
  Biochemistry, 39, 2593-2602.  
10985782 J.K.McBee, V.Kuksa, R.Alvarez, Lera, O.Prezhdo, F.Haeseleer, I.Sokal, and K.Palczewski (2000).
Isomerization of all-trans-retinol to cis-retinols in bovine retinal pigment epithelial cells: dependence on the specificity of retinoid-binding proteins.
  Biochemistry, 39, 11370-11380.  
11111077 T.R.Tansey, and I.Shechter (2000).
Structure and regulation of mammalian squalene synthase.
  Biochim Biophys Acta, 1529, 49-62.  
  9882662 C.M.Apfel, B.Takács, M.Fountoulakis, M.Stieger, and W.Keck (1999).
Use of genomics to identify bacterial undecaprenyl pyrophosphate synthetase: cloning, expression, and characterization of the essential uppS gene.
  J Bacteriol, 181, 483-492.  
10099534 C.W.Wang, M.K.Oh, and J.C.Liao (1999).
Engineered isoprenoid pathway enhances astaxanthin production in Escherichia coli.
  Biotechnol Bioeng, 62, 235-241.  
10542413 K.Wang, and S.Ohnuma (1999).
Chain-length determination mechanism of isoprenyl diphosphate synthases and implications for molecular evolution.
  Trends Biochem Sci, 24, 445-451.  
10489461 M.Fujihashi, N.Shimizu, Y.W.Zhang, T.Koyama, and K.Miki (1999).
Crystallization and preliminary X-ray diffraction studies of undecaprenyl diphosphate synthase from Micrococcus luteus B-P 26.
  Acta Crystallogr D Biol Crystallogr, 55, 1606-1607.  
9914250 C.A.Lesburg, J.M.Caruthers, C.M.Paschall, and D.W.Christianson (1998).
Managing and manipulating carbocations in biology: terpenoid cyclase structure and mechanism.
  Curr Opin Struct Biol, 8, 695-703.  
9539701 J.Bohlmann, G.Meyer-Gauen, and R.Croteau (1998).
Plant terpenoid synthases: molecular biology and phylogenetic analysis.
  Proc Natl Acad Sci U S A, 95, 4126-4133.  
9618485 J.Bohlmann, J.Crock, R.Jetter, and R.Croteau (1998).
Terpenoid-based defenses in conifers: cDNA cloning, characterization, and functional expression of wound-inducible (E)-alpha-bisabolene synthase from grand fir (Abies grandis).
  Proc Natl Acad Sci U S A, 95, 6756-6761.  
9519404 K.U.Wendt, and G.E.Schulz (1998).
Isoprenoid biosynthesis: manifold chemistry catalyzed by similar enzymes.
  Structure, 6, 127-133.  
9375250 C.A.Townsend (1997).
Structural studies of natural product biosynthetic proteins.
  Chem Biol, 4, 721-730.  
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.