1G9D

CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN B COMPLEXED WITH AN INHIBITOR (EXPERIMENT 2)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.263 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

A Novel Mechanism for Clostridium botulinum Neurotoxin Inhibition

Eswaramoorthy, S.Kumaran, D.Swaminathan, S.

(2002) Biochemistry 41: 9795-9802

  • DOI: https://doi.org/10.1021/bi020060c
  • Primary Citation of Related Structures:  
    1G9A, 1G9B, 1G9C, 1G9D

  • PubMed Abstract: 

    Clostridium botulinum neurotoxins are zinc endopeptidase proteins responsible for cleaving specific peptide bonds of proteins of neuroexocytosis apparatus. The ability of drugs to interfere with toxin's catalytic activity is being evaluated with zinc chelators and metalloprotease inhibitors. It is important to develop effective pharmacological treatment for the intact holotoxin before the catalytic domain separates and enters the cytosol. We present here evidence for a novel mechanism of an inhibitor binding to the holotoxin and for the chelation of zinc from our structural studies on Clostridium botulinum neurotoxin type B in complex with a potential metalloprotease inhibitor, bis(5-amidino-2-benzimidazolyl)methane, and provide snapshots of the reaction as it progresses. The binding and inhibition mechanism of this inhibitor to the neurotoxin seems to be unique for intact botulinum neurotoxins. The environment of the active site rearranges in the presence of the inhibitor, and the zinc ion is gradually removed from the active site and transported to a different site in the protein, probably causing loss of catalytic activity.


  • Organizational Affiliation

    Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BOTULINUM NEUROTOXIN TYPE B1,290Clostridium botulinumMutation(s): 0 
EC: 3.4.24.69
UniProt
Find proteins for P10844 (Clostridium botulinum)
Explore P10844 
Go to UniProtKB:  P10844
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10844
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
BAB Binding MOAD:  1G9D IC50: 7500 (nM) from 1 assay(s)
PDBBind:  1G9D IC50: 5000 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.263 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 76.65α = 90
b = 123.28β = 112.92
c = 95.69γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-11-13
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-09
    Changes: Data collection, Database references, Derived calculations, Refinement description