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PDBsum entry 1ee0

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1ee0
Jmol
Contents
Protein chains
376 a.a. *
Ligands
CAA ×2
Waters ×541
* Residue conservation analysis
PDB id:
1ee0
Name: Transferase
Title: 2-pyrone synthase complexed with acetoacetyl-coa
Structure: 2-pyrone synthase. Chain: a, b. Engineered: yes
Source: Gerbera hybrid cultivar. Organism_taxid: 18101. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.05Å     R-factor:   0.189     R-free:   0.243
Authors: J.M.Jez,M.B.Austin,J.Ferrer,M.E.Bowmann,J.Schroeder,J.P.Noel
Key ref:
J.M.Jez et al. (2000). Structural control of polyketide formation in plant-specific polyketide synthases. Chem Biol, 7, 919-930. PubMed id: 11137815 DOI: 10.1016/S1074-5521(00)00041-7
Date:
28-Jan-00     Release date:   31-Jan-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P48391  (2PS_GERHY) -  2-pyrone synthase
Seq:
Struc:
402 a.a.
376 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   2 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
DOI no: 10.1016/S1074-5521(00)00041-7 Chem Biol 7:919-930 (2000)
PubMed id: 11137815  
 
 
Structural control of polyketide formation in plant-specific polyketide synthases.
J.M.Jez, M.B.Austin, J.Ferrer, M.E.Bowman, J.Schröder, J.P.Noel.
 
  ABSTRACT  
 
BACKGROUND: Polyketide synthases (PKSs) generate molecular diversity by utilizing different starter molecules and by controlling the final length of the polyketide. Although exploitation of this mechanistic variability has produced novel polyketides, the structural foundation of this versatility is unclear. Plant-specific PKSs are essential for the biosynthesis of anti-microbial phytoalexins, anthocyanin floral pigments, and inducers of Rhizobium nodulation genes. 2-Pyrone synthase (2-PS) and chalcone synthase (CHS) are plant-specific PKSs that share 74% amino acid sequence identity. 2-PS forms the triketide methylpyrone from an acetyl-CoA starter molecule and two malonyl-CoAs. CHS uses a p-coumaroyl-CoA starter molecule and three malonyl-CoAs to produce the tetraketide chalcone. Our goal was to elucidate the molecular basis of starter molecule selectivity and control of polyketide length in this class of PKS.Results: The 2.05 A resolution crystal structure of 2-PS complexed with the reaction intermediate acetoacetyl-CoA was determined by molecular replacement. 2-PS and CHS share a common three-dimensional fold, a set of conserved catalytic residues, and similar CoA binding sites. However, the active site cavity of 2-PS is smaller than the cavity in CHS. Of the 28 residues lining the 2-PS initiation/elongation cavity, four positions vary in CHS. Point mutations at three of these positions in CHS (T197L, G256L, and S338I) altered product formation. Combining these mutations in a CHS triple mutant (T197L/G256L/S338I) yielded an enzyme that was functionally identical to 2-PS.Conclusions: Structural and functional characterization of 2-PS together with generation of a CHS mutant with an initiation/elongation cavity analogous to 2-PS demonstrates that cavity volume influences the choice of starter molecule and controls the final length of the polyketide. These results provide a structural basis for control of polyketide length in other PKSs, and suggest strategies for further increasing the scope of polyketide biosynthetic diversity.
 
  Selected figure(s)  
 
Figure 4.
Fig. 4. 2-PS–acetoacetyl-CoA complex. (a) Stereo-view of the acetoacetyl-CoA binding site. The orientation is the same as in Figure 2. The SIGMAA-weighted |2F[o]−F[c]| electron density (1.2 σ) for acetoacetyl-CoA and the oxidized catalytic cysteine is shown in blue cage. (b) Schematic of interactions between 2-PS and acetoacetyl-CoA. Hydrogen bonds are indicated with distances in Å.
Figure 5.
Fig. 5. Proposed 2-PS reaction mechanism.
 
  The above figures are reprinted by permission from Cell Press: Chem Biol (2000, 7, 919-930) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20878179 S.Koskela, P.P.Söderholm, M.Ainasoja, T.Wennberg, K.D.Klika, V.V.Ovcharenko, I.Kylänlahti, T.Auerma, J.Yli-Kauhaluoma, K.Pihlaja, P.M.Vuorela, and T.H.Teeri (2011).
Polyketide derivatives active against Botrytis cinerea in Gerbera hybrida.
  Planta, 233, 37-48.  
20348430 D.Cook, A.M.Rimando, T.E.Clemente, J.Schröder, F.E.Dayan, N.P.Nanayakkara, Z.Pan, B.P.Noonan, M.Fishbein, I.Abe, S.O.Duke, and S.R.Baerson (2010).
Alkylresorcinol synthases expressed in Sorghum bicolor root hairs play an essential role in the biosynthesis of the allelopathic benzoquinone sorgoleone.
  Plant Cell, 22, 867-887.  
20080733 H.Morita, Y.Shimokawa, M.Tanio, R.Kato, H.Noguchi, S.Sugio, T.Kohno, and I.Abe (2010).
A structure-based mechanism for benzalacetone synthase from Rheum palmatum.
  Proc Natl Acad Sci U S A, 107, 669-673.
PDB codes: 3a5q 3a5r 3a5s
20358127 I.Abe, and H.Morita (2010).
Structure and function of the chalcone synthase superfamily of plant type III polyketide synthases.
  Nat Prod Rep, 27, 809-838.  
19876746 P.K.Koduri, G.S.Gordon, E.I.Barker, C.C.Colpitts, N.W.Ashton, and D.Y.Suh (2010).
Genome-wide analysis of the chalcone synthase superfamily genes of Physcomitrella patens.
  Plant Mol Biol, 72, 247-263.  
19043702 K.V.Kiselev, A.S.Dubrovina, and V.P.Bulgakov (2009).
Phenylalanine ammonia-lyase and stilbene synthase gene expression in rolB transgenic cell cultures of Vitis amurensis.
  Appl Microbiol Biotechnol, 82, 647-655.  
19710020 T.Klundt, M.Bocola, M.Lütge, T.Beuerle, B.Liu, and L.Beerhues (2009).
A single amino acid substitution converts benzophenone synthase into phenylpyrone synthase.
  J Biol Chem, 284, 30957-30964.  
19348024 Y.Mizuuchi, S.P.Shi, K.Wanibuchi, A.Kojima, H.Morita, H.Noguchi, and I.Abe (2009).
Novel type III polyketide synthases from Aloe arborescens.
  FEBS J, 276, 2391-2401.  
  18323613 C.Taguchi, F.Taura, T.Tamada, Y.Shoyama, Y.Shoyama, H.Tanaka, R.Kuroki, and S.Morimoto (2008).
Crystallization and preliminary X-ray diffraction studies of polyketide synthase-1 (PKS-1) from Cannabis sativa.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 217-220.  
  18391433 H.Morita, M.Tanio, S.Kondo, R.Kato, K.Wanibuchi, H.Noguchi, S.Sugio, I.Abe, and T.Kohno (2008).
Crystallization and preliminary crystallographic analysis of a plant type III polyketide synthase that produces benzalacetone.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 304-306.  
18981598 I.Abe (2008).
Engineering of plant polyketide biosynthesis.
  Chem Pharm Bull (Tokyo), 56, 1505-1514.  
18347585 M.B.Austin, P.E.O'Maille, and J.P.Noel (2008).
Evolving biosynthetic tangos negotiate mechanistic landscapes.
  Nat Chem Biol, 4, 217-222.  
18476876 O.Yu, and J.M.Jez (2008).
Nature's assembly line: biosynthesis of simple phenylpropanoids and polyketides.
  Plant J, 54, 750-762.  
18940668 S.B.Rubin-Pitel, H.Zhang, T.Vu, J.S.Brunzelle, H.Zhao, and S.K.Nair (2008).
Distinct structural elements dictate the specificity of the type III pentaketide synthase from Neurospora crassa.
  Chem Biol, 15, 1079-1090.
PDB codes: 3euo 3euq 3eut
19043200 Y.Mizuuchi, Y.Shimokawa, K.Wanibuchi, H.Noguchi, and I.Abe (2008).
Structure function analysis of novel type III polyketide synthases from Arabidopsis thaliana.
  Biol Pharm Bull, 31, 2205-2210.  
17268612 C.Hertweck, A.Luzhetskyy, Y.Rebets, and A.Bechthold (2007).
Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork.
  Nat Prod Rep, 24, 162-190.  
  17620714 H.Morita, S.Kondo, R.Kato, K.Wanibuchi, H.Noguchi, S.Sugio, I.Abe, and T.Kohno (2007).
Crystallization and preliminary crystallographic analysis of an acridone-producing novel multifunctional type III polyketide synthase from Huperzia serrata.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 576-578.  
17462571 H.Morita, S.Kondo, S.Oguro, H.Noguchi, S.Sugio, I.Abe, and T.Kohno (2007).
Structural insight into chain-length control and product specificity of pentaketide chromone synthase from Aloe arborescens.
  Chem Biol, 14, 359-369.
PDB codes: 2d3m 2d51 2d52
17229146 K.Springob, S.Samappito, A.Jindaprasert, J.Schmidt, J.E.Page, W.De-Eknamkul, and T.M.Kutchan (2007).
A polyketide synthase of Plumbago indica that catalyzes the formation of hexaketide pyrones.
  FEBS J, 274, 406-417.  
17250741 K.Wanibuchi, P.Zhang, T.Abe, H.Morita, T.Kohno, G.Chen, H.Noguchi, and I.Abe (2007).
An acridone-producing novel multifunctional type III polyketide synthase from Huperzia serrata.
  FEBS J, 274, 1073-1082.  
17482864 K.Watanabe, A.P.Praseuth, and C.C.Wang (2007).
A comprehensive and engaging overview of the type III family of polyketide synthases.
  Curr Opin Chem Biol, 11, 279-286.  
17331946 S.Li, S.Grüschow, J.S.Dordick, and D.H.Sherman (2007).
Molecular analysis of the role of tyrosine 224 in the active site of Streptomyces coelicolor RppA, a bacterial type III polyketide synthase.
  J Biol Chem, 282, 12765-12772.  
16356722 A.M.Haapalainen, G.Meriläinen, and R.K.Wierenga (2006).
The thiolase superfamily: condensing enzymes with diverse reaction specificities.
  Trends Biochem Sci, 31, 64-71.  
16575575 C.D.Dana, D.R.Bevan, and B.S.Winkel (2006).
Molecular modeling of the effects of mutant alleles on chalcone synthase protein structure.
  J Mol Model, 12, 905-914.  
16245348 D.Xie, Z.Shao, J.Achkar, W.Zha, J.W.Frost, and H.Zhao (2006).
Microbial synthesis of triacetic acid lactone.
  Biotechnol Bioeng, 93, 727-736.  
  16946474 H.Morita, S.Kondo, T.Abe, H.Noguchi, S.Sugio, I.Abe, and T.Kohno (2006).
Crystallization and preliminary crystallographic analysis of a novel plant type III polyketide synthase that produces pentaketide chromone.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 899-901.  
16367761 I.Abe, T.Watanabe, W.Lou, and H.Noguchi (2006).
Active site residues governing substrate selectivity and polyketide chain length in aloesone synthase.
  FEBS J, 273, 208-218.  
16551366 K.T.Watts, P.C.Lee, and C.Schmidt-Dannert (2006).
Biosynthesis of plant-specific stilbene polyketides in metabolically engineered Escherichia coli.
  BMC Biotechnol, 6, 22.  
16906151 M.B.Austin, T.Saito, M.E.Bowman, S.Haydock, A.Kato, B.S.Moore, R.R.Kay, and J.P.Noel (2006).
Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase.
  Nat Chem Biol, 2, 494-502.
PDB code: 2h84
16496097 S.Brand, D.Hölscher, A.Schierhorn, A.Svatos, J.Schröder, and B.Schneider (2006).
A type III polyketide synthase from Wachendorfia thyrsiflora and its role in diarylheptanoid and phenylphenalenone biosynthesis.
  Planta, 224, 413-428.  
16850408 T.H.Teeri, P.Elomaa, M.Kotilainen, and V.A.Albert (2006).
Mining plant diversity: Gerbera as a model system for plant developmental and biosynthetic research.
  Bioessays, 28, 756-767.  
16931521 W.Zha, S.B.Rubin-Pitel, and H.Zhao (2006).
Characterization of the substrate specificity of PhlD, a type III polyketide synthase from Pseudomonas fluorescens.
  J Biol Chem, 281, 32036-32047.  
16501309 A.Ageez, Y.Kazama, R.Sugiyama, and S.Kawano (2005).
Male-fertility genes expressed in male flower buds of Silene latifolia include homologs of anther-specific genes.
  Genes Genet Syst, 80, 403-413.  
15930622 X.Ma, J.Koepke, A.Bayer, G.Fritzsch, H.Michel, and J.Stöckigt (2005).
Crystallization and preliminary X-ray analysis of native and selenomethionyl vinorine synthase from Rauvolfia serpentina.
  Acta Crystallogr D Biol Crystallogr, 61, 694-696.  
15324811 A.Watanabe, and Y.Ebizuka (2004).
Unprecedented mechanism of chain length determination in fungal aromatic polyketide synthases.
  Chem Biol, 11, 1101-1106.  
15725058 B.S.Winkel (2004).
Metabolic channeling in plants.
  Annu Rev Plant Biol, 55, 85.  
15265863 M.B.Austin, M.Izumikawa, M.E.Bowman, D.W.Udwary, J.L.Ferrer, B.S.Moore, and J.P.Noel (2004).
Crystal structure of a bacterial type III polyketide synthase and enzymatic control of reactive polyketide intermediates.
  J Biol Chem, 279, 45162-45174.
PDB code: 1u0m
15377220 R.A.Dixon (2004).
Phytoestrogens.
  Annu Rev Plant Biol, 55, 225-261.  
15286723 R.Sankaranarayanan, P.Saxena, U.B.Marathe, R.S.Gokhale, V.M.Shanmugam, and R.Rukmini (2004).
A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites.
  Nat Struct Mol Biol, 11, 894-900.
PDB codes: 1ted 1tee
15604692 V.Hemleben, A.Dressel, B.Epping, R.Lukacin, S.Martens, and M.Austin (2004).
Characterization and structural features of a chalcone synthase mutation in a white-flowering line of Matthiola incana R. Br. (Brassicaceae).
  Plant Mol Biol, 55, 455-465.  
12795704 B.Liu, H.Falkenstein-Paul, W.Schmidt, and L.Beerhues (2003).
Benzophenone synthase and chalcone synthase from Hypericum androsaemum cell cultures: cDNA cloning, functional expression, and site-directed mutagenesis of two polyketide synthases.
  Plant J, 34, 847-855.  
  12889743 C.D.Reeves (2003).
The enzymology of combinatorial biosynthesis.
  Crit Rev Biotechnol, 23, 95.  
12514126 G.Sciara, S.G.Kendrew, A.E.Miele, N.G.Marsh, L.Federici, F.Malatesta, G.Schimperna, C.Savino, and B.Vallone (2003).
The structure of ActVA-Orf6, a novel type of monooxygenase involved in actinorhodin biosynthesis.
  EMBO J, 22, 205-215.
PDB codes: 1lq9 1n5q 1n5s 1n5t 1n5v
12724310 I.Abe, Y.Sano, Y.Takahashi, and H.Noguchi (2003).
Site-directed mutagenesis of benzalacetone synthase. The role of the Phe215 in plant type III polyketide synthases.
  J Biol Chem, 278, 25218-25226.  
12866053 J.H.Dawe, C.T.Porter, J.M.Thornton, and A.B.Tabor (2003).
A template search reveals mechanistic similarities and differences in beta-ketoacyl synthases (KAS) and related enzymes.
  Proteins, 52, 427-435.  
12941968 P.Saxena, G.Yadav, D.Mohanty, and R.S.Gokhale (2003).
A new family of type III polyketide synthases in Mycobacterium tuberculosis.
  J Biol Chem, 278, 44780-44790.  
11880657 A.Kodan, H.Kuroda, and F.Sakai (2002).
A stilbene synthase from Japanese red pine (Pinus densiflora): implications for phytoalexin accumulation and down-regulation of flavonoid biosynthesis.
  Proc Natl Acad Sci U S A, 99, 3335-3339.  
12193782 H.J.Kwon, W.C.Smith, A.J.Scharon, S.H.Hwang, M.J.Kurth, and B.Shen (2002).
C-O bond formation by polyketide synthases.
  Science, 297, 1327-1330.  
12429097 H.Pan, S.Tsai, E.S.Meadows, L.J.Miercke, A.T.Keatinge-Clay, J.O'Connell, C.Khosla, and R.M.Stroud (2002).
Crystal structure of the priming beta-ketosynthase from the R1128 polyketide biosynthetic pathway.
  Structure, 10, 1559-1568.
PDB code: 1mzj
11959984 J.M.Jez, M.E.Bowman, and J.P.Noel (2002).
Expanding the biosynthetic repertoire of plant type III polyketide synthases by altering starter molecule specificity.
  Proc Natl Acad Sci U S A, 99, 5319-5324.
PDB code: 1jwx
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.