PDBsum entry 1tee

Go to PDB code: 
protein Protein-protein interface(s) links
Transferase PDB id
Protein chains
368 a.a. *
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of c205f mutant of pks18 from mycobacteriu tuberculosis
Structure: Pks18. Chain: a, b, c, d. Synonym: polyketide synthase. Engineered: yes. Mutation: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Gene: pks18. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
2.90Å     R-factor:   0.221     R-free:   0.258
Authors: R.Sankaranarayanan,V.M.Shanmugam,R.Rukmini
Key ref:
R.Sankaranarayanan et al. (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. PubMed id: 15286723 DOI: 10.1038/nsmb809
25-May-04     Release date:   03-Aug-04    
Go to PROCHECK summary

Protein chains
P9WPF1  (PKS18_MYCTU) -  Alpha-pyrone synthesis polyketide synthase-like Pks18
393 a.a.
368 a.a.*
Key:    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   6 terms 
  Biochemical function     catalytic activity     4 terms  


DOI no: 10.1038/nsmb809 Nat Struct Mol Biol 11:894-900 (2004)
PubMed id: 15286723  
A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites.
R.Sankaranarayanan, P.Saxena, U.B.Marathe, R.S.Gokhale, V.M.Shanmugam, R.Rukmini.
The superfamily of plant and bacterial type III polyketide synthases (PKSs) produces diverse metabolites with distinct biological functions. PKS18, a type III PKS from Mycobacterium tuberculosis, displays an unusual broad specificity for aliphatic long-chain acyl-coenzyme A (acyl-CoA) starter units (C(6)-C(20)) to produce tri- and tetraketide pyrones. The crystal structure of PKS18 reveals a 20 A substrate binding tunnel, hitherto unidentified in this superfamily of enzymes. This remarkable tunnel extends from the active site to the surface of the protein and is primarily generated by subtle changes of backbone dihedral angles in the core of the protein. Mutagenic studies combined with structure determination provide molecular insights into the structural elements that contribute to the chain length specificity of the enzyme. This first bacterial type III PKS structure underlines a fascinating example of the way in which subtle changes in protein architecture can generate metabolite diversity in nature.
  Selected figure(s)  
Figure 1.
Figure 1. A schematic diagram of the reaction catalyzed by PKS18.
Figure 5.
Figure 5. C205F mutant structure. A closeup view of the residues surrounding the substrate binding tunnel shown in a stereo representation. The phenylalanine residue is shown with the electron density, a 2F[o] - F[c] map contoured at 1.2 , along with a stick model of the myristic acid moiety as observed in the wild type structure. Figure was prepared using SETOR34.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2004, 11, 894-900) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
21041675 H.Morita, K.Wanibuchi, H.Nii, R.Kato, S.Sugio, and I.Abe (2010).
Structural basis for the one-pot formation of the diarylheptanoid scaffold by curcuminoid synthase from Oryza sativa.
  Proc Natl Acad Sci U S A, 107, 19778-19783.
PDB code: 3ale
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.  
19557027 A.Miyanaga, and S.Horinouchi (2009).
Enzymatic synthesis of bis-5-alkylresorcinols by resorcinol-producing type III polyketide synthases.
  J Antibiot (Tokyo), 62, 371-376.  
19296440 B.Taneja, J.Yadav, T.K.Chakraborty, and S.K.Brahmachari (2009).
An Indian effort towards affordable drugs: "generic to designer drugs".
  Biotechnol J, 4, 348-360.  
19465653 C.Nakano, H.Ozawa, G.Akanuma, N.Funa, and S.Horinouchi (2009).
Biosynthesis of aliphatic polyketides by type III polyketide synthase and methyltransferase in Bacillus subtilis.
  J Bacteriol, 191, 4916-4923.  
19177221 I.Fujii (2009).
Heterologous expression systems for polyketide synthases.
  Nat Prod Rep, 26, 155-169.  
18252726 R.Ghosh, A.Chhabra, P.A.Phatale, S.K.Samrat, J.Sharma, A.Gosain, D.Mohanty, S.Saran, and R.S.Gokhale (2008).
Dissecting the functional role of polyketide synthases in Dictyostelium discoideum: biosynthesis of the differentiation regulating factor 4-methyl-5-pentylbenzene-1,3-diol.
  J Biol Chem, 283, 11348-11354.  
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.  
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.  
17374612 N.Funa, T.Awakawa, and S.Horinouchi (2007).
Pentaketide resorcylic acid synthesis by type III polyketide synthase from Neurospora crassa.
  J Biol Chem, 282, 14476-14481.  
17592143 P.Kumar, M.W.Schelle, M.Jain, F.L.Lin, C.J.Petzold, M.D.Leavell, J.A.Leary, J.S.Cox, and C.R.Bertozzi (2007).
PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1.
  Proc Natl Acad Sci U S A, 104, 11221-11226.  
17389997 R.S.Gokhale, P.Saxena, T.Chopra, and D.Mohanty (2007).
Versatile polyketide enzymatic machinery for the biosynthesis of complex mycobacterial lipids.
  Nat Prod Rep, 24, 267-277.  
17935970 R.S.Gokhale, R.Sankaranarayanan, and D.Mohanty (2007).
Versatility of polyketide synthases in generating metabolic diversity.
  Curr Opin Struct Biol, 17, 736-743.  
17440908 S.Grüschow, T.J.Buchholz, W.Seufert, J.S.Dordick, and D.H.Sherman (2007).
Substrate profile analysis and ACP-mediated acyl transfer in Streptomyces coelicolor Type III polyketide synthases.
  Chembiochem, 8, 863-868.  
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.  
16395556 F.Gross, N.Luniak, O.Perlova, N.Gaitatzis, H.Jenke-Kodama, K.Gerth, D.Gottschalk, E.Dittmann, and R.Müller (2006).
Bacterial type III polyketide synthases: phylogenetic analysis and potential for the production of novel secondary metabolites by heterologous expression in pseudomonads.
  Arch Microbiol, 185, 28-38.  
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.  
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
16597676 N.Funa, H.Ozawa, A.Hirata, and S.Horinouchi (2006).
Phenolic lipid synthesis by type III polyketide synthases is essential for cyst formation in Azotobacter vinelandii.
  Proc Natl Acad Sci U S A, 103, 6356-6361.  
16921353 R.Sankaranarayanan (2006).
A type III PKS makes the DIFference.
  Nat Chem Biol, 2, 451-452.  
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.  
15860421 J.P.Noel, M.B.Austin, and E.K.Bomati (2005).
Structure-function relationships in plant phenylpropanoid biosynthesis.
  Curr Opin Plant Biol, 8, 249-253.  
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 code is shown on the right.