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PDBsum entry 2z5l

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protein links
Transferase PDB id
2z5l
Jmol
Contents
Protein chain
453 a.a. *
Waters ×103
* Residue conservation analysis
PDB id:
2z5l
Name: Transferase
Title: The first ketoreductase of the tylosin pks
Structure: Tylactone synthase starter module and modules 1 & chain: a. Fragment: residues in database 1962- 2451. Synonym: tylkr1. Engineered: yes
Source: Streptomyces fradiae. Organism_taxid: 1906. Gene: tylg. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.95Å     R-factor:   0.259     R-free:   0.287
Authors: A.T.Keatinge-Clay,R.M.Stroud
Key ref: A.T.Keatinge-Clay (2007). A tylosin ketoreductase reveals how chirality is determined in polyketides. Chem Biol, 14, 898-908. PubMed id: 17719489
Date:
14-Jul-07     Release date:   28-Aug-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O33954  (O33954_STRFR) -  Tylactone synthase starter module and modules 1 & 2
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Seq:
Struc:
4472 a.a.
453 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
Chem Biol 14:898-908 (2007)
PubMed id: 17719489  
 
 
A tylosin ketoreductase reveals how chirality is determined in polyketides.
A.T.Keatinge-Clay.
 
  ABSTRACT  
 
Because it controls the majority of polyketide stereocenters, the ketoreductase (KR) is a central target in engineering polyketide synthases (PKSs). To elucidate the mechanisms of stereocontrol, the structure of KR from the first module of the tylosin PKS was determined. A comparison with a recently solved erythromycin KR that operates on the same substrate explains why their products have opposite alpha-substituent chiralities. The structure reveals how polyketides are guided into the active site by key residues in different KR types. There are four types of reductase-competent KRs, each capable of fixing a unique combination of alpha-substituent and beta-hydroxyl group chiralities, as well as two types of reductase-incompetent KRs that control alpha-substituent chirality alone. A protocol to assign how a module will enforce substituent chirality based on its sequence is presented.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21338915 A.J.Hughes, and A.Keatinge-Clay (2011).
Enzymatic extender unit generation for in vitro polyketide synthase reactions: structural and functional showcasing of Streptomyces coelicolor MatB.
  Chem Biol, 18, 165-176.
PDB codes: 3nyq 3nyr
21340070 D.H.Kwan, M.Tosin, N.Schläger, F.Schulz, and P.F.Leadlay (2011).
Insights into the stereospecificity of ketoreduction in a modular polyketide synthase.
  Org Biomol Chem, 9, 2053-2056.  
21444795 L.Laureti, L.Song, S.Huang, C.Corre, P.Leblond, G.L.Challis, and B.Aigle (2011).
Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens.
  Proc Natl Acad Sci U S A, 108, 6258-6263.  
  21472957 O.Vergnolle, F.Hahn, A.Baerga-Ortiz, P.F.Leadlay, and J.N.Andexer (2011).
Stereoselectivity of isolated dehydratase domains of the borrelidin polyketide synthase: implications for cis double bond formation.
  Chembiochem, 12, 1011-1014.  
20589823 F.Kudo, A.Motegi, K.Mizoue, and T.Eguchi (2010).
Cloning and characterization of the biosynthetic gene cluster of 16-membered macrolide antibiotic FD-891: involvement of a dual functional cytochrome P450 monooxygenase catalyzing epoxidation and hydroxylation.
  Chembiochem, 11, 1574-1582.  
20696392 J.Zheng, C.A.Taylor, S.K.Piasecki, and A.T.Keatinge-Clay (2010).
Structural and functional analysis of A-type ketoreductases from the amphotericin modular polyketide synthase.
  Structure, 18, 913-922.
PDB codes: 3mjc 3mje 3mjs 3mjt 3mjv
20444870 S.Anand, M.V.Prasad, G.Yadav, N.Kumar, J.Shehara, M.Z.Ansari, and D.Mohanty (2010).
SBSPKS: structure based sequence analysis of polyketide synthases.
  Nucleic Acids Res, 38, W487-W496.  
20534347 W.Ding, C.Lei, Q.He, Q.Zhang, Y.Bi, and W.Liu (2010).
Insights into bacterial 6-methylsalicylic acid synthase and its engineering to orsellinic acid synthase for spirotetronate generation.
  Chem Biol, 17, 495-503.  
20426415 Y.Luo, W.Li, J.Ju, Q.Yuan, N.R.Peters, F.M.Hoffmann, S.X.Huang, T.S.Bugni, S.Rajski, H.Osada, and B.Shen (2010).
Functional characterization of TtnD and TtnF, unveiling new insights into tautomycetin biosynthesis.
  J Am Chem Soc, 132, 6663-6671.  
19636447 A.Koglin, and C.T.Walsh (2009).
Structural insights into nonribosomal peptide enzymatic assembly lines.
  Nat Prod Rep, 26, 987.  
19129623 A.Migita, M.Watanabe, Y.Hirose, K.Watanabe, T.Tokiwano, H.Kinashi, and H.Oikawa (2009).
Identification of a gene cluster of polyether antibiotic lasalocid from Streptomyces lasaliensis.
  Biosci Biotechnol Biochem, 73, 169-176.  
19301315 C.Li, K.E.Roege, and W.L.Kelly (2009).
Analysis of the indanomycin biosynthetic gene cluster from Streptomyces antibioticus NRRL 8167.
  Chembiochem, 10, 1064-1072.  
19151726 E.J.Brignole, S.Smith, and F.J.Asturias (2009).
Conformational flexibility of metazoan fatty acid synthase enables catalysis.
  Nat Struct Mol Biol, 16, 190-197.  
19201253 P.Bernhardt, and S.E.O'Connor (2009).
Opportunities for enzyme engineering in natural product biosynthesis.
  Curr Opin Chem Biol, 13, 35-42.  
19832975 P.Goldstein, J.Zucko, D.Vujaklija, A.Krisko, D.Hranueli, P.F.Long, C.Etchebest, B.Basrak, and J.Cullum (2009).
Clustering of protein domains for functional and evolutionary studies.
  BMC Bioinformatics, 10, 335.  
19362634 S.C.Tsai, and B.D.Ames (2009).
Structural enzymology of polyketide synthases.
  Methods Enzymol, 459, 17-47.  
18978015 A.Starcevic, J.Zucko, J.Simunkovic, P.F.Long, J.Cullum, and D.Hranueli (2008).
ClustScan: an integrated program package for the semi-automatic annotation of modular biosynthetic gene clusters and in silico prediction of novel chemical structures.
  Nucleic Acids Res, 36, 6882-6892.  
19022183 D.H.Kwan, Y.Sun, F.Schulz, H.Hong, B.Popovic, J.C.Sim-Stark, S.F.Haydock, and P.F.Leadlay (2008).
Prediction and manipulation of the stereochemistry of enoylreduction in modular polyketide synthases.
  Chem Biol, 15, 1231-1240.  
18586939 J.Fang, Y.Zhang, L.Huang, X.Jia, Q.Zhang, X.Zhang, G.Tang, and W.Liu (2008).
Cloning and characterization of the tetrocarcin A gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics.
  J Bacteriol, 190, 6014-6025.  
18357594 K.J.Weissman, and R.Müller (2008).
Protein-protein interactions in multienzyme megasynthetases.
  Chembiochem, 9, 826-848.  
19011750 K.L.Kavanagh, H.Jörnvall, B.Persson, and U.Oppermann (2008).
Medium- and short-chain dehydrogenase/reductase gene and protein families : the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes.
  Cell Mol Life Sci, 65, 3895-3906.  
18937219 L.Kellenberger, I.S.Galloway, G.Sauter, G.Böhm, U.Hanefeld, J.Cortés, J.Staunton, and P.F.Leadlay (2008).
A polylinker approach to reductive loop swaps in modular polyketide synthases.
  Chembiochem, 9, 2740-2749.  
18948193 M.Leibundgut, T.Maier, S.Jenni, and N.Ban (2008).
The multienzyme architecture of eukaryotic fatty acid synthases.
  Curr Opin Struct Biol, 18, 714-725.  
18635006 Q.Zhao, Q.He, W.Ding, M.Tang, Q.Kang, Y.Yu, W.Deng, Q.Zhang, J.Fang, G.Tang, and W.Liu (2008).
Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis.
  Chem Biol, 15, 693-705.  
18772430 T.Maier, M.Leibundgut, and N.Ban (2008).
The crystal structure of a mammalian fatty acid synthase.
  Science, 321, 1315-1322.
PDB codes: 2vz8 2vz9
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.