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Isomerase PDB id
1kzn
Jmol
Contents
Protein chain
186 a.a. *
Ligands
CBN
Waters ×164
* Residue conservation analysis
PDB id:
1kzn
Name: Isomerase
Title: Crystal structure of e. Coli 24kda domain in complex with clorobiocin
Structure: DNA gyrase subunit b. Chain: a. Fragment: 24 kda n-terminus domain. Synonym: gyrase b. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.30Å     R-factor:   0.239     R-free:   0.267
Authors: D.Lafitte,V.Lamour,P.O.Tsvetkov,A.A.Makarov,M.Klich, P.Deprez,D.Moras,C.Briand,R.Gilli
Key ref:
D.Lafitte et al. (2002). DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose. Biochemistry, 41, 7217-7223. PubMed id: 12044152 DOI: 10.1021/bi0159837
Date:
07-Feb-02     Release date:   19-Jun-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0AES6  (GYRB_ECOLI) -  DNA gyrase subunit B
Seq:
Struc: 		 
Seq:
Struc: 		804 a.a.
186 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.5.99.1.3  - Dna topoisomerase (ATP-hydrolyzing).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP-dependent breakage, passage and rejoining of double-stranded DNA.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     chromosome   1 term 
  Biological process     DNA topological change   1 term 
  Biochemical function     DNA binding     3 terms  

 

 
DOI no: 10.1021/bi0159837 Biochemistry 41:7217-7223 (2002)
PubMed id: 12044152  
 
 
DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose.
D.Lafitte, V.Lamour, P.O.Tsvetkov, A.A.Makarov, M.Klich, P.Deprez, D.Moras, C.Briand, R.Gilli.
 
  ABSTRACT  
 
DNA gyrase is a major bacterial protein that is involved in replication and transcription and catalyzes the negative supercoiling of bacterial circular DNA. DNA gyrase is a known target for antibacterial agents since its blocking induces bacterial death. Quinolones, coumarins, and cyclothialidines have been designed to inhibit gyrase. Significant improvements can still be envisioned for a better coumarin-gyrase interaction. In this work, we obtained the crystal costructures of the natural coumarin clorobiocin and a synthetic analogue with the 24 kDa gyrase fragment. We used isothermal titration microcalorimetry and differential scanning calorimetry to obtain the thermodynamic parameters representative of the molecular interactions occurring during the binding process between coumarins and the 24 kDa gyrase fragment. We provide the first experimental evidence that clorobiocin binds gyrase with a stronger affinity than novobiocin. We also demonstrate the crucial role of both the hydroxybenzoate isopentenyl moiety and the 5'-alkyl group on the noviose of the coumarins in the binding affinity for gyrase.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21530019 L.Saíz-Urra, M...Cabrera Pérez, A.M.Helguera, and M.Froeyen (2011).
Combining molecular docking and QSAR studies for modelling the antigyrase activity of cyclothialidine derivatives.
  Eur J Med Chem, 46, 2736-2747.  
20107862 D.Calligaris, P.Verdier-Pinard, F.Devred, C.Villard, D.Braguer, and D.Lafitte (2010).
Microtubule targeting agents: from biophysics to proteomics.
  Cell Mol Life Sci, 67, 1089-1104.  
20941729 S.Boyapati, U.Kulandaivelu, S.Sangu, and M.R.Vanga (2010).
Synthesis, antimicrobial evaluation, and docking studies of novel 4-substituted quinazoline derivatives as DNA-gyrase inhibitors.
  Arch Pharm (Weinheim), 343, 570-576.  
19779639 L.Heide (2009).
The aminocoumarins: biosynthesis and biology.
  Nat Prod Rep, 26, 1241-1250.  
19267450 L.J.Juszczak, and R.Z.Desamero (2009).
Extension of the tryptophan chi2,1 dihedral angle-W3 band frequency relationship to a full rotation: correlations and caveats.
  Biochemistry, 48, 2777-2787.  
  19007043 A.Kotsiou, E.Diamanti, A.Potamianou, H.Parara, J.Vovou, C.Perisanidis, C.Tes, and C.Tesseromatis (2008).
Anticoagulant-induced changes on antibiotic concentrations in the serum and bones.
  Eur J Drug Metab Pharmacokinet, 33, 173-179.  
18347114 C.Anderle, M.Stieger, M.Burrell, S.Reinelt, A.Maxwell, M.Page, and L.Heide (2008).
Biological activities of novel gyrase inhibitors of the aminocoumarin class.
  Antimicrob Agents Chemother, 52, 1982-1990.  
18588888 F.Devred, P.O.Tsvetkov, P.Barbier, D.Allegro, S.B.Horwitz, A.A.Makarov, and V.Peyrot (2008).
Stathmin/Op18 is a novel mediator of vinblastine activity.
  FEBS Lett, 582, 2484-2488.  
18093089 L.A.Plesniak, K.Botsch, M.Leibrand, M.Kelly, D.Sem, J.A.Adams, and P.Jennings (2008).
Transferred NOE and saturation transfer difference NMR studies of novobiocin binding to EnvZ suggest binding mode similar to DNA gyrase.
  Chem Biol Drug Des, 71, 28-35.  
17682095 D.A.Ostrov, J.A.Hernández Prada, P.E.Corsino, K.A.Finton, N.Le, and T.C.Rowe (2007).
Discovery of novel DNA gyrase inhibitors by high-throughput virtual screening.
  Antimicrob Agents Chemother, 51, 3688-3698.  
16485005 M.A.Fischbach, H.Lin, D.R.Liu, and C.T.Walsh (2006).
How pathogenic bacteria evade mammalian sabotage in the battle for iron.
  Nat Chem Biol, 2, 132-138.  
16914449 V.A.Mitkevich, A.V.Kononenko, I.Y.Petrushanko, D.V.Yanvarev, A.A.Makarov, and L.L.Kisselev (2006).
Termination of translation in eukaryotes is mediated by the quaternary eRF1*eRF3*GTP*Mg2+ complex. The biological roles of eRF3 and prokaryotic RF3 are profoundly distinct.
  Nucleic Acids Res, 34, 3947-3954.  
15853944 S.S.Garrido, A.C.Scatigno, E.Trovatti, D.C.Carvalho, and R.Marchetto (2005).
Probing the binding of the coumarin drugs using peptide fragments of DNA gyrase B protein.
  J Pept Res, 65, 502-511.  
15556007 A.S.Eustáquio, B.Gust, S.M.Li, S.Pelzer, W.Wohlleben, K.F.Chater, and L.Heide (2004).
Production of 8'-halogenated and 8'-unsubstituted novobiocin derivatives in genetically engineered streptomyces coelicolor strains.
  Chem Biol, 11, 1561-1572.  
15123279 U.Galm, M.A.Dessoy, J.Schmidt, L.A.Wessjohann, and L.Heide (2004).
In vitro and in vivo production of new aminocoumarins by a combined biochemical, genetic, and synthetic approach.
  Chem Biol, 11, 173-183.  
15047534 U.Galm, S.Heller, S.Shapiro, M.Page, S.M.Li, and L.Heide (2004).
Antimicrobial and DNA gyrase-inhibitory activities of novel clorobiocin derivatives produced by mutasynthesis.
  Antimicrob Agents Chemother, 48, 1307-1312.  
  12670542 A.S.Eustáquio, B.Gust, T.Luft, S.M.Li, K.F.Chater, and L.Heide (2003).
Clorobiocin biosynthesis in Streptomyces: identification of the halogenase and generation of structural analogs.
  Chem Biol, 10, 279-288.  
12777382 F.Pojer, R.Kahlich, B.Kammerer, S.M.Li, and L.Heide (2003).
CloR, a bifunctional non-heme iron oxygenase involved in clorobiocin biosynthesis.
  J Biol Chem, 278, 30661-30668.  
14732929 M.J.Cliff, and J.E.Ladbury (2003).
A survey of the year 2002 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 16, 383-391.  
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.