spacer
spacer

PDBsum entry 1i1e
Go to PDB code: 
protein ligands metals links
Hydrolase PDB id
1i1e

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chain
1287 a.a. *
Ligands
DM2
SO4
Metals
_ZN
Waters ×354
* Residue conservation analysis
PDB id:
1i1e
Name: Hydrolase
Title: Crystal structure of clostridium botulinum neurotoxin b complexed with doxorubicin
Structure: Botulinum neurotoxin type b. Chain: a. Synonym: bontoxilysin b. Ec: 3.4.24.69
Source: Clostridium botulinum. Organism_taxid: 1491
Resolution:
2.50Å     R-factor:   0.217     R-free:   0.276
Authors: S.Eswaramoorthy,D.Kumaran,S.Swaminathan
Key ref:
S.Eswaramoorthy et al. (2001). Crystallographic evidence for doxorubicin binding to the receptor-binding site in Clostridium botulinum neurotoxin B. Acta Crystallogr D Biol Crystallogr, 57, 1743-1746. PubMed id: 11679763 DOI: 10.1107/S0907444901013531
Date:
01-Feb-01     Release date:   21-Nov-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10844  (BXB_CLOBO) -  Botulinum neurotoxin type B from Clostridium botulinum
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1291 a.a.
1287 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.24.69  - bontoxilysin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on small molecule substrates.
      Cofactor: Zn(2+)

 

 
DOI no: 10.1107/S0907444901013531 Acta Crystallogr D Biol Crystallogr 57:1743-1746 (2001)
PubMed id: 11679763  
 
 
Crystallographic evidence for doxorubicin binding to the receptor-binding site in Clostridium botulinum neurotoxin B.
S.Eswaramoorthy, D.Kumaran, S.Swaminathan.
 
  ABSTRACT  
 
The neurotoxins of Clostridium botulinum and tetanus bind to gangliosides as a first step of their toxin activity. Identifying suitable receptors that compete with gangliosides could prevent toxin binding to the neuronal cells. A possible ganglioside-binding site of the botulinum neurotoxin B (BoNT/B) has already been proposed and evidence is now presented for a drug binding to botulinum neurotoxin B from structural studies. Doxorubicin, a well known DNA intercalator, binds to the neurotoxin at the receptor-binding site proposed earlier. The structure of the BoNT/B-doxorubicin complex reveals that doxorubicin has interactions with the neurotoxin similar to those of sialyllactose. The aglycone moiety of the doxorubicin stacks with tryptophan 1261 and interacts with histidine 1240 of the binding domain. Here, the possibility is presented of designing a potential antagonist for these neurotoxins from crystallographic analysis of the neurotoxin-doxorubicin complex, which will be an excellent lead compound.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 (a) The numbering scheme of doxorubicin. (b) Stereoview of the interactions of doxorubicin with the protein. Hydrogen-bonding contacts are shown as dashed lines. While amino-acid residues interacting with doxorubicin are shown as a stick model, doxorubicin is shown as a ball-and-stick model.
 
  The above figure is reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2001, 57, 1743-1746) copyright 2001.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21149386 C.Garcia-Rodriguez, I.N.Geren, J.Lou, F.Conrad, C.Forsyth, W.Wen, S.Chakraborti, H.Zao, G.Manzanarez, T.J.Smith, J.Brown, W.H.Tepp, N.Liu, S.Wijesuriya, M.T.Tomic, E.A.Johnson, L.A.Smith, and J.D.Marks (2011).
Neutralizing human monoclonal antibodies binding multiple serotypes of botulinum neurotoxin.
  Protein Eng Des Sel, 24, 321-331.  
20233039 M.Montal (2010).
Botulinum neurotoxin: a marvel of protein design.
  Annu Rev Biochem, 79, 591-617.  
20877571 N.Gul, L.A.Smith, and S.A.Ahmed (2010).
Light chain separated from the rest of the type a botulinum neurotoxin molecule is the most catalytically active form.
  PLoS One, 5, e12872.  
19164566 A.Fischer, Y.Nakai, L.M.Eubanks, C.M.Clancy, W.H.Tepp, S.Pellett, T.J.Dickerson, E.A.Johnson, K.D.Janda, and M.Montal (2009).
Bimodal modulation of the botulinum neurotoxin protein-conducting channel.
  Proc Natl Acad Sci U S A, 106, 1330-1335.  
17429823 B.M.McArdle, and R.J.Quinn (2007).
Identification of protein fold topology shared between different folds inhibited by natural products.
  Chembiochem, 8, 788-798.  
18075579 J.A.Wells, and C.L.McClendon (2007).
Reaching for high-hanging fruit in drug discovery at protein-protein interfaces.
  Nature, 450, 1001-1009.  
17059824 R.Levy, C.M.Forsyth, S.L.LaPorte, I.N.Geren, L.A.Smith, and J.D.Marks (2007).
Fine and domain-level epitope mapping of botulinum neurotoxin type A neutralizing antibodies by yeast surface display.
  J Mol Biol, 365, 196-210.  
17167421 R.Jin, A.Rummel, T.Binz, and A.T.Brunger (2006).
Botulinum neurotoxin B recognizes its protein receptor with high affinity and specificity.
  Nature, 444, 1092-1095.
PDB code: 2nm1
15803193 J.C.Burnett, E.A.Henchal, A.L.Schmaljohn, and S.Bavari (2005).
The evolving field of biodefence: therapeutic developments and diagnostics.
  Nat Rev Drug Discov, 4, 281-297.  
15123599 A.Rummel, T.Karnath, T.Henke, H.Bigalke, and T.Binz (2004).
Synaptotagmins I and II act as nerve cell receptors for botulinum neurotoxin G.
  J Biol Chem, 279, 30865-30870.  
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.

 

spacer
spacer