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PDBsum entry 1xr3
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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1xr3

 

 

 

 

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Contents
Protein chains
256 a.a. *
Ligands
NAP ×2
ISZ ×2
* Residue conservation analysis
PDB id:
1xr3
Name: Oxidoreductase
Title: Actinorhodin polyketide ketoreductase with NADP and the inhibitor isoniazid bound
Structure: Actinorhodin polyketide ketoreductase. Chain: a, b. Engineered: yes
Source: Streptomyces coelicolor. Organism_taxid: 1902. Gene: actiii. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.71Å     R-factor:   0.212     R-free:   0.256
Authors: T.P.Korman,J.A.Hill,T.N.Vu,S.C.Tsai
Key ref:
T.P.Korman et al. (2004). Structural analysis of actinorhodin polyketide ketoreductase: cofactor binding and substrate specificity. Biochemistry, 43, 14529-14538. PubMed id: 15544323 DOI: 10.1021/bi048133a
Date:
13-Oct-04     Release date:   27-Sep-05    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P16544  (ACT3_STRCO) -  Putative ketoacyl reductase from Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
Seq:
Struc: 		261 a.a.
256 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.3.1.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1021/bi048133a Biochemistry 43:14529-14538 (2004)
PubMed id: 15544323  
 
 
Structural analysis of actinorhodin polyketide ketoreductase: cofactor binding and substrate specificity.
T.P.Korman, J.A.Hill, T.N.Vu, S.C.Tsai.
 
  ABSTRACT  
 
Aromatic polyketides are a class of natural products that include many pharmaceutically important aromatic compounds. Understanding the structure and function of PKS will provide clues to the molecular basis of polyketide biosynthesis specificity. Polyketide chain reduction by ketoreductase (KR) provides regio- and stereochemical diversity. Two cocrystal structures of actinorhodin polyketide ketoreductase (act KR) were solved to 2.3 A with either the cofactor NADP(+) or NADPH bound. The monomer fold is a highly conserved Rossmann fold. Subtle differences between structures of act KR and fatty acid KRs fine-tune the tetramer interface and substrate binding pocket. Comparisons of the NADP(+)- and NADPH-bound structures indicate that the alpha6-alpha7 loop region is highly flexible. The intricate proton-relay network in the active site leads to the proposed catalytic mechanism involving four waters, NADPH, and the active site tetrad Asn114-Ser144-Tyr157-Lys161. Acyl carrier protein and substrate docking models shed light on the molecular basis of KR regio- and stereoselectivity, as well as the differences between aromatic polyketide and fatty acid biosyntheses. Sequence comparison indicates that the above features are highly conserved among aromatic polyketide KRs. The structures of act KR provide an important step toward understanding aromatic PKS and will enhance our ability to design novel aromatic polyketide natural products with different reduction patterns.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20352666 C.Olano, C.Méndez, and J.A.Salas (2010).
Post-PKS tailoring steps in natural product-producing actinomycetes from the perspective of combinatorial biosynthesis.
  Nat Prod Rep, 27, 571-616.  
20358042 H.Zhou, Y.Li, and Y.Tang (2010).
Cyclization of aromatic polyketides from bacteria and fungi.
  Nat Prod Rep, 27, 839-868.  
19292437 A.Das, and C.Khosla (2009).
Biosynthesis of aromatic polyketides in bacteria.
  Acc Chem Res, 42, 631-639.  
19942143 A.Das, and C.Khosla (2009).
In vivo and in vitro analysis of the hedamycin polyketide synthase.
  Chem Biol, 16, 1197-1207.  
19636447 A.Koglin, and C.T.Walsh (2009).
Structural insights into nonribosomal peptide enzymatic assembly lines.
  Nat Prod Rep, 26, 987.  
19362634 S.C.Tsai, and B.D.Ames (2009).
Structural enzymology of polyketide synthases.
  Methods Enzymol, 459, 17-47.  
19726666 S.K.Lim, J.Ju, E.Zazopoulos, H.Jiang, J.W.Seo, Y.Chen, Z.Feng, S.R.Rajski, C.M.Farnet, and B.Shen (2009).
iso-Migrastatin, migrastatin, and dorrigocin production in Streptomyces platensis NRRL 18993 is governed by a single biosynthetic machinery featuring an acyltransferase-less type I polyketide synthase.
  J Biol Chem, 284, 29746-29756.  
18388203 B.D.Ames, T.P.Korman, W.Zhang, P.Smith, T.Vu, Y.Tang, and S.C.Tsai (2008).
Crystal structure and functional analysis of tetracenomycin ARO/CYC: implications for cyclization specificity of aromatic polyketides.
  Proc Natl Acad Sci U S A, 105, 5349-5354.
PDB codes: 2rer 2res 2rez
19022176 G.Castaldo, J.Zucko, S.Heidelberger, D.Vujaklija, D.Hranueli, J.Cullum, P.Wattana-Amorn, M.P.Crump, J.Crosby, and P.F.Long (2008).
Proposed arrangement of proteins forming a bacterial type II polyketide synthase.
  Chem Biol, 15, 1156-1165.  
18072779 S.M.Ma, J.Zhan, X.Xie, K.Watanabe, Y.Tang, and W.Zhang (2008).
Redirecting the cyclization steps of fungal polyketide synthase.
  J Am Chem Soc, 130, 38-39.  
18940666 T.Oja, K.Palmu, H.Lehmussola, O.Leppäranta, K.Hännikäinen, J.Niemi, P.Mäntsälä, and M.Metsä-Ketelä (2008).
Characterization of the alnumycin gene cluster reveals unusual gene products for pyran ring formation and dioxan biosynthesis.
  Chem Biol, 15, 1046-1057.  
18205400 T.P.Korman, Y.H.Tan, J.Wong, R.Luo, and S.C.Tsai (2008).
Inhibition kinetics and emodin cocrystal structure of a type II polyketide ketoreductase.
  Biochemistry, 47, 1837-1847.
PDB codes: 2rh4 2rhc 2rhr
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.  
17328673 C.Khosla, Y.Tang, A.Y.Chen, N.A.Schnarr, and D.E.Cane (2007).
Structure and mechanism of the 6-deoxyerythronolide B synthase.
  Annu Rev Biochem, 76, 195-221.  
17898897 S.Smith, and S.C.Tsai (2007).
The type I fatty acid and polyketide synthases: a tale of two megasynthases.
  Nat Prod Rep, 24, 1041-1072.  
17631493 W.Zhang, K.Watanabe, C.C.Wang, and Y.Tang (2007).
Investigation of early tailoring reactions in the oxytetracycline biosynthetic pathway.
  J Biol Chem, 282, 25717-25725.  
16710331 J.J.Kohler (2006).
A century at the chemistry-biology interface.
  Nat Chem Biol, 2, 288-292.  
16597959 W.Zhang, B.D.Ames, S.C.Tsai, and Y.Tang (2006).
Engineered biosynthesis of a novel amidated polyketide, using the malonamyl-specific initiation module from the oxytetracycline polyketide synthase.
  Appl Environ Microbiol, 72, 2573-2580.  
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.

 

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