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protein ligands metals links
Cell cycle PDB id
2r75
Jmol
Contents
Protein chain
323 a.a. *
Ligands
01G
Metals
_MG
Waters ×283
* Residue conservation analysis
PDB id:
2r75
Name: Cell cycle
Title: Aquifex aeolicus ftsz with 8-morpholino-gtp
Structure: Cell division protein ftsz. Chain: 1. Engineered: yes
Source: Aquifex aeolicus. Organism_taxid: 63363. Strain: vf5. Gene: ftsz. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: gene cloned into ndei/hindiii restriction sites
Resolution:
1.40Å     R-factor:   0.139     R-free:   0.184
Authors: T.Lappchen,V.A.Pinas,A.F.Hartog,G.J.Koomen,C.Schaffner- Barbero,J.M.Andreu,D.Trambaiolo,J.Lowe,A.Juhem,A.V.Popov, T.Den Blaauwen
Key ref: T.Läppchen et al. (2008). Probing FtsZ and tubulin with C8-substituted GTP analogs reveals differences in their nucleotide binding sites. Chem Biol, 15, 189-199. PubMed id: 18291323 DOI: 10.1016/j.chembiol.2007.12.013
Date:
07-Sep-07     Release date:   22-Jul-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O66809  (FTSZ_AQUAE) -  Cell division protein FtsZ
Seq:
Struc: 		367 a.a.
323 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     protein complex   3 terms 
  Biological process     microtubule-based process   5 terms 
  Biochemical function     nucleotide binding     3 terms  

 

 
DOI no: 10.1016/j.chembiol.2007.12.013 Chem Biol 15:189-199 (2008)
PubMed id: 18291323  
 
 
Probing FtsZ and tubulin with C8-substituted GTP analogs reveals differences in their nucleotide binding sites.
T.Läppchen, V.A.Pinas, A.F.Hartog, G.J.Koomen, C.Schaffner-Barbero, J.M.Andreu, D.Trambaiolo, J.Löwe, A.Juhem, A.V.Popov, T.den Blaauwen.
 
  ABSTRACT  
 
The cytoskeletal proteins, FtsZ and tubulin, play a pivotal role in prokaryotic cell division and eukaryotic chromosome segregation, respectively. Selective inhibitors of the GTP-dependent polymerization of FtsZ could constitute a new class of antibiotics, while several inhibitors of tubulin are widely used in antiproliferative therapy. In this work, we set out to identify selective inhibitors of FtsZ based on the structure of its natural ligand, GTP. We found that GTP analogs with small hydrophobic substituents at C8 of the nucleobase efficiently inhibit FtsZ polymerization, whereas they have an opposite effect on the polymerization of tubulin. The inhibitory activity of the GTP analogs on FtsZ polymerization allowed us to crystallize FtsZ in complex with C8-morpholino-GTP, revealing the binding mode of a GTP derivative containing a nonmodified triphosphate chain.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21413908 D.Awasthi, K.Kumar, and I.Ojima (2011).
Therapeutic potential of FtsZ inhibition: a patent perspective.
  Expert Opin Ther Pat, 21, 657-679.  
20559630 J.Hritz, T.Läppchen, and C.Oostenbrink (2010).
Calculations of binding affinity between C8-substituted GTP analogs and the bacterial cell-division protein FtsZ.
  Eur Biophys J, 39, 1573-1580.  
20149104 J.Strömqvist, K.Skoog, D.O.Daley, J.Widengren, and G.von Heijne (2010).
Estimating Z-ring radius and contraction in dividing Escherichia coli.
  Mol Microbiol, 76, 151-158.  
19470504 L.I.Llarrull, J.F.Fisher, and S.Mobashery (2009).
Molecular basis and phenotype of methicillin resistance in Staphylococcus aureus and insights into new beta-lactams that meet the challenge.
  Antimicrob Agents Chemother, 53, 4051-4063.  
18291311 W.Vollmer (2008).
Targeting the bacterial Z-ring.
  Chem Biol, 15, 93-94.  
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.