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PDBsum entry 1i88

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protein ligands links
Transferase PDB id
1i88
Jmol
Contents
Protein chains
389 a.a. *
Ligands
SO4 ×2
Waters ×752
* Residue conservation analysis
PDB id:
1i88
Name: Transferase
Title: Chalcone synthase (g256v)
Structure: Chalcone synthase 2. Chain: a, b. Synonym: chs2. Engineered: yes. Mutation: yes
Source: Medicago sativa. Organism_taxid: 3879. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
1.45Å     R-factor:   0.203     R-free:   0.221
Authors: J.M.Jez,M.E.Bowman,J.P.Noel
Key ref:
J.M.Jez et al. (2001). Structure-guided programming of polyketide chain-length determination in chalcone synthase. Biochemistry, 40, 14829-14838. PubMed id: 11732902 DOI: 10.1021/bi015621z
Date:
12-Mar-01     Release date:   12-Dec-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P30074  (CHS2_MEDSA) -  Chalcone synthase 2
Seq:
Struc:
389 a.a.
389 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.3.1.74  - Naringenin-chalcone synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Chalcone and Stilbene Biosynthesis
      Reaction: 3 malonyl-CoA + 4-coumaroyl-CoA = 4 CoA + naringenin chalcone + 3 CO2
3 × malonyl-CoA
+ 4-coumaroyl-CoA
= 4 × CoA
+ naringenin chalcone
+ 3 × CO(2)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi015621z Biochemistry 40:14829-14838 (2001)
PubMed id: 11732902  
 
 
Structure-guided programming of polyketide chain-length determination in chalcone synthase.
J.M.Jez, M.E.Bowman, J.P.Noel.
 
  ABSTRACT  
 
Chalcone synthase (CHS) belongs to the family of type III polyketide synthases (PKS) that catalyze formation of structurally diverse polyketides. CHS synthesizes a tetraketide by sequential condensation of three acetyl anions derived from malonyl-CoA decarboxylation to a p-coumaroyl moiety attached to an active site cysteine. Gly256 resides on the surface of the CHS active site that is in direct contact with the polyketide chain derived from malonyl-CoA. Thus, position 256 serves as an ideal target to probe the link between cavity volume and polyketide chain-length determination in type III PKS. Functional examination of CHS G256A, G256V, G256L, and G256F mutants reveals altered product profiles from that of wild-type CHS. With p-coumaroyl-CoA as a starter molecule, the G256A and G256V mutants produce notably more tetraketide lactone. Further restrictions in cavity volume such as that seen in the G256L and G256F mutants yield increasing levels of the styrylpyrone bis-noryangonin from a triketide intermediate. X-ray crystallographic structures of the CHS G256A, G256V, G256L, and G256F mutants establish that these substitutions reduce the size of the active site cavity without significant alterations in the conformations of the polypeptide backbones. The side chain volume of position 256 influences both the number of condensation reactions during polyketide chain extension and the conformation of the triketide and tetraketide intermediates during the cyclization reaction. These results viewed in conjunction with the natural sequence variation of residue 256 suggest that rapid diversification of product specificity without concomitant loss of substantial catalytic activity in related CHS-like enzymes can occur by site-specific evolution of side chain volume at position 256.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
19530704 M.Wang, H.Zhou, M.Wirz, Y.Tang, and C.N.Boddy (2009).
A thioesterase from an iterative fungal polyketide synthase shows macrocyclization and cross coupling activity and may play a role in controlling iterative cycling through product offloading.
  Biochemistry, 48, 6288-6290.  
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.  
18476861 B.J.Nikolau, M.A.Perera, L.Brachova, and B.Shanks (2008).
Platform biochemicals for a biorenewable chemical industry.
  Plant J, 54, 536-545.  
18981598 I.Abe (2008).
Engineering of plant polyketide biosynthesis.
  Chem Pharm Bull (Tokyo), 56, 1505-1514.  
18476876 O.Yu, and J.M.Jez (2008).
Nature's assembly line: biosynthesis of simple phenylpropanoids and polyketides.
  Plant J, 54, 750-762.  
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.  
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.  
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.  
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
15932991 H.Jiang, K.V.Wood, and J.A.Morgan (2005).
Metabolic engineering of the phenylpropanoid pathway in Saccharomyces cerevisiae.
  Appl Environ Microbiol, 71, 2962-2969.  
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
  12889743 C.D.Reeves (2003).
The enzymology of combinatorial biosynthesis.
  Crit Rev Biotechnol, 23, 95.  
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.  
12470730 N.L.Pohl (2002).
Nonnatural substrates for polyketide synthases and their associated modifying enzymes.
  Curr Opin Chem Biol, 6, 773-778.  
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.