spacer
spacer

PDBsum entry 2a97
Go to PDB code: 
protein metals Protein-protein interface(s) links
Hydrolase PDB id
2a97

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
392 a.a. *
Metals
_CD ×7
_ZN ×2
Waters ×241
* Residue conservation analysis
PDB id:
2a97
Name: Hydrolase
Title: Crystal structure of catalytic domain of clostridium botulinum neurotoxin serotype f
Structure: Botulinum neurotoxin type f. Chain: a, b. Fragment: catalytic domain, light chain. Synonym: bont/f. Bontoxilysin f. Serotype f light chain. Engineered: yes
Source: Clostridium botulinum. Organism_taxid: 1491. Strain: nctc 10821. Gene: botf. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.80Å     R-factor:   0.241     R-free:   0.269
Authors: R.Agarwal,T.Binz,S.Swaminathan
Key ref:
R.Agarwal et al. (2005). Structural analysis of botulinum neurotoxin serotype F light chain: implications on substrate binding and inhibitor design. Biochemistry, 44, 11758-11765. PubMed id: 16128577 DOI: 10.1021/bi0510072
Date:
11-Jul-05     Release date:   20-Sep-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P30996  (BXF_CLOBO) -  Botulinum neurotoxin type F from Clostridium botulinum
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1274 a.a.
392 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: 10.1021/bi0510072 Biochemistry 44:11758-11765 (2005)
PubMed id: 16128577  
 
 
Structural analysis of botulinum neurotoxin serotype F light chain: implications on substrate binding and inhibitor design.
R.Agarwal, T.Binz, S.Swaminathan.
 
  ABSTRACT  
 
The seven serologically distinct Clostridium botulinum neurotoxins (BoNTs A-G) are zinc endopeptidases which block the neurotransmitter release by cleaving one of the three proteins of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptor complex (SNARE complex) essential for the fusion of vesicles containing neurotransmitters with target membranes. These metallopeptidases exhibit unique specificity for the substrates and peptide bonds they cleave. Development of countermeasures and therapeutics for BoNTs is a priority because of their extreme toxicity and potential misuse as biowarfare agents. Though they share sequence homology and structural similarity, the structural information on each one of them is required to understand the mechanism of action of all of them because of their specificity. Unraveling the mechanism will help in the ultimate goal of developing inhibitors as antibotulinum drugs for the toxins. Here, we report the high-resolution structure of active BoNT/F catalytic domain in two crystal forms. The structure was exploited for modeling the substrate binding and identifying the S1' subsite and the putative exosites which are different from BoNT/A or BoNT/B. The orientation of docking of the substrate at the active site is consistent with the experimental BoNT/A-LC:SNAP-25 peptide model and our proposed model for BoNT/E-LC:SNAP-25.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21078393 G.Masuyer, M.Beard, V.A.Cadd, J.A.Chaddock, and K.R.Acharya (2011).
Structure and activity of a functional derivative of Clostridium botulinum neurotoxin B.
  J Struct Biol, 174, 52-57.
PDB code: 2xhl
20233039 M.Montal (2010).
Botulinum neurotoxin: a marvel of protein design.
  Annu Rev Biochem, 79, 591-617.  
20169001 Y.Fujinaga (2010).
Interaction of botulinum toxin with the epithelial barrier.
  J Biomed Biotechnol, 2010, 974943.  
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.  
19290051 M.C.Scotcher, J.A.McGarvey, E.A.Johnson, and L.H.Stanker (2009).
Epitope characterization and variable region sequence of f1-40, a high-affinity monoclonal antibody to botulinum neurotoxin type a (Hall strain).
  PLoS ONE, 4, e4924.  
19111565 M.Montal (2009).
Translocation of botulinum neurotoxin light chain protease by the heavy chain protein-conducting channel.
  Toxicon, 54, 565-569.  
19543288 R.Agarwal, J.J.Schmidt, R.G.Stafford, and S.Swaminathan (2009).
Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F.
  Nat Struct Mol Biol, 16, 789-794.
PDB codes: 3fie 3fii
18032388 A.Fischer, C.Garcia-Rodriguez, I.Geren, J.Lou, J.D.Marks, T.Nakagawa, and M.Montal (2008).
Molecular architecture of botulinum neurotoxin E revealed by single particle electron microscopy.
  J Biol Chem, 283, 3997-4003.  
18789058 B.R.Eapen (2008).
Molecular biology of botulinum neurotoxin serotype A: a cosmetic perspective.
  J Cosmet Dermatol, 7, 221-225.  
18434312 D.Kumaran, R.Rawat, M.L.Ludivico, S.A.Ahmed, and S.Swaminathan (2008).
Structure- and substrate-based inhibitor design for Clostridium botulinum neurotoxin serotype A.
  J Biol Chem, 283, 18883-18891.
PDB codes: 3bwi 3c88 3c89 3c8a 3c8b
18658150 R.Agarwal, and S.Swaminathan (2008).
SNAP-25 substrate peptide (residues 180-183) binds to but bypasses cleavage by catalytically active Clostridium botulinum neurotoxin E.
  J Biol Chem, 283, 25944-25951.
PDB code: 3d3x
18213512 S.A.Ahmed, M.A.Olson, M.L.Ludivico, J.Gilsdorf, and L.A.Smith (2008).
Identification of residues surrounding the active site of type A botulinum neurotoxin important for substrate recognition and catalytic activity.
  Protein J, 27, 151-162.  
17666397 A.Fischer, and M.Montal (2007).
Crucial role of the disulfide bridge between botulinum neurotoxin light and heavy chains in protease translocation across membranes.
  J Biol Chem, 282, 29604-29611.  
17907800 A.T.Brunger, M.A.Breidenbach, R.Jin, A.Fischer, J.S.Santos, and M.Montal (2007).
Botulinum neurotoxin heavy chain belt as an intramolecular chaperone for the light chain.
  PLoS Pathog, 3, 1191-1194.  
17524984 N.R.Silvaggi, G.E.Boldt, M.S.Hixon, J.P.Kennedy, S.Tzipori, K.D.Janda, and K.N.Allen (2007).
Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain complexed with small-molecule inhibitors highlight active-site flexibility.
  Chem Biol, 14, 533-542.
PDB codes: 2ilp 2ima 2imb 2imc
17244603 S.Chen, J.J.Kim, and J.T.Barbieri (2007).
Mechanism of substrate recognition by botulinum neurotoxin serotype A.
  J Biol Chem, 282, 9621-9627.  
17112720 P.R.Mittl, and M.G.Grütter (2006).
Opportunities for structure-based design of protease-directed drugs.
  Curr Opin Struct Biol, 16, 769-775.  
16478727 S.Chen, and J.T.Barbieri (2006).
Unique substrate recognition by botulinum neurotoxins serotypes A and E.
  J Biol Chem, 281, 10906-10911.  
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