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Isomerase PDB id
1s16
Jmol
Contents
Protein chains
380 a.a. *
Ligands
SO4 ×2
ANP ×2
Metals
_MG ×2
Waters ×247
* Residue conservation analysis
PDB id:
1s16
Name: Isomerase
Title: Crystal structure of e. Coli topoisomerase iv pare 43kda sub complexed with adpnp
Structure: Topoisomerase iv subunit b. Chain: a, b. Fragment: 43kda subunit. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: pare, nfxd, b3030. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.224     R-free:   0.240
Authors: Y.Wei,C.H.Gross
Key ref: S.Bellon et al. (2004). Crystal structures of Escherichia coli topoisomerase IV ParE subunit (24 and 43 kilodaltons): a single residue dictates differences in novobiocin potency against topoisomerase IV and DNA gyrase. Antimicrob Agents Chemother, 48, 1856-1864. PubMed id: 15105144 DOI: 10.1128/AAC.48.5.1856-1864.2004
Date:
05-Jan-04     Release date:   04-May-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P20083  (PARE_ECOLI) -  DNA topoisomerase 4 subunit B
Seq:
Struc: 		 
Seq:
Struc: 		630 a.a.
380 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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: 10.1128/AAC.48.5.1856-1864.2004 Antimicrob Agents Chemother 48:1856-1864 (2004)
PubMed id: 15105144  
 
 
Crystal structures of Escherichia coli topoisomerase IV ParE subunit (24 and 43 kilodaltons): a single residue dictates differences in novobiocin potency against topoisomerase IV and DNA gyrase.
S.Bellon, J.D.Parsons, Y.Wei, K.Hayakawa, L.L.Swenson, P.S.Charifson, J.A.Lippke, R.Aldape, C.H.Gross.
 
  ABSTRACT  
 
Topoisomerase IV and DNA gyrase are related bacterial type II topoisomerases that utilize the free energy from ATP hydrolysis to catalyze topological changes in the bacterial genome. The essential function of DNA gyrase is the introduction of negative DNA supercoils into the genome, whereas the essential function of topoisomerase IV is to decatenate daughter chromosomes following replication. Here, we report the crystal structures of a 43-kDa N-terminal fragment of Escherichia coli topoisomerase IV ParE subunit complexed with adenylyl-imidodiphosphate at 2.0-A resolution and a 24-kDa N-terminal fragment of the ParE subunit complexed with novobiocin at 2.1-A resolution. The solved ParE structures are strikingly similar to the known gyrase B (GyrB) subunit structures. We also identified single-position equivalent amino acid residues in ParE (M74) and in GyrB (I78) that, when exchanged, increased the potency of novobiocin against topoisomerase IV by nearly 20-fold (to 12 nM). The corresponding exchange in gyrase (I78 M) yielded a 20-fold decrease in the potency of novobiocin (to 1.0 micro M). These data offer an explanation for the observation that novobiocin is significantly less potent against topoisomerase IV than against DNA gyrase. Additionally, the enzyme kinetic parameters were affected. In gyrase, the ATP K(m) increased approximately 5-fold and the V(max) decreased approximately 30%. In contrast, the topoisomerase IV ATP K(m) decreased by a factor of 6, and the V(max) increased approximately 2-fold from the wild-type values. These data demonstrate that the ParE M74 and GyrB I78 side chains impart opposite effects on the enzyme's substrate affinity and catalytic efficiency.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21103609 F.P.Davis (2011).
Proteome-wide prediction of overlapping small molecule and protein binding sites using structure.
  Mol Biosyst, 7, 545-557.  
20165898 C.Sissi, and M.Palumbo (2010).
In front of and behind the replication fork: bacterial type IIA topoisomerases.
  Cell Mol Life Sci, 67, 2001-2024.  
  19920922 O.Doppelt-Azeroual, F.Moriaud, F.Delfaud, and A.G.de Brevern (2009).
Analysis of HSP90-related folds with MED-SuMo classification approach.
  Drug Des Devel Ther, 3, 59-72.  
19208647 P.Forterre, and D.Gadelle (2009).
Phylogenomics of DNA topoisomerases: their origin and putative roles in the emergence of modern organisms.
  Nucleic Acids Res, 37, 679-692.  
19564360 X.S.Pan, K.A.Gould, and L.M.Fisher (2009).
Probing the differential interactions of quinazolinedione PD 0305970 and quinolones with gyrase and topoisomerase IV.
  Antimicrob Agents Chemother, 53, 3822-3831.  
18755053 A.J.Schoeffler, and J.M.Berger (2008).
DNA topoisomerases: harnessing and constraining energy to govern chromosome topology.
  Q Rev Biophys, 41, 41.  
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.  
18647240 N.D.Thomsen, and J.M.Berger (2008).
Structural frameworks for considering microbial protein- and nucleic acid-dependent motor ATPases.
  Mol Microbiol, 69, 1071-1090.  
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.  
17375187 I.Laponogov, D.A.Veselkov, M.K.Sohi, X.S.Pan, A.Achari, C.Yang, J.D.Ferrara, L.M.Fisher, and M.R.Sanderson (2007).
Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target.
  PLoS ONE, 2, e301.
PDB code: 2nov
17159922 L.L.Silver (2007).
Multi-targeting by monotherapeutic antibacterials.
  Nat Rev Drug Discov, 6, 41-55.  
17116675 T.H.Grossman, D.J.Bartels, S.Mullin, C.H.Gross, J.D.Parsons, Y.Liao, A.L.Grillot, D.Stamos, E.R.Olson, P.S.Charifson, and N.Mani (2007).
Dual targeting of GyrB and ParE by a novel aminobenzimidazole class of antibacterial compounds.
  Antimicrob Agents Chemother, 51, 657-666.  
16635801 J.J.Barker (2006).
Antibacterial drug discovery and structure-based design.
  Drug Discov Today, 11, 391-404.  
16569833 N.Mani, C.H.Gross, J.D.Parsons, B.Hanzelka, U.Müh, S.Mullin, Y.Liao, A.L.Grillot, D.Stamos, P.S.Charifson, and T.H.Grossman (2006).
In vitro characterization of the antibacterial spectrum of novel bacterial type II topoisomerase inhibitors of the aminobenzimidazole class.
  Antimicrob Agents Chemother, 50, 1228-1237.  
15939019 K.D.Corbett, and J.M.Berger (2005).
Structural dissection of ATP turnover in the prototypical GHL ATPase TopoVI.
  Structure, 13, 873-882.
PDB codes: 1z59 1z5a 1z5b 1z5c
16321962 K.Yamashiro, and A.Yamagishi (2005).
Characterization of the DNA gyrase from the thermoacidophilic archaeon Thermoplasma acidophilum.
  J Bacteriol, 187, 8531-8536.  
15372084 M.B.Schmid (2004).
Seeing is believing: the impact of structural genomics on antimicrobial drug discovery.
  Nat Rev Microbiol, 2, 739-746.  
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.