RCSB PDB - 1XTG: Crystal structure of NEUROTOXIN BONT/A complexed with Synaptosomal-associated protein 25

 1XTG

Crystal structure of NEUROTOXIN BONT/A complexed with Synaptosomal-associated protein 25


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.218 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Substrate recognition strategy for botulinum neurotoxin serotype A

Breidenbach, M.A.Brunger, A.T.

(2004) Nature 432: 925-929

  • DOI: https://doi.org/10.1038/nature03123
  • Primary Citation of Related Structures:  
    1XTF, 1XTG

  • PubMed Abstract: 

    Clostridal neurotoxins (CNTs) are the causative agents of the neuroparalytic diseases botulism and tetanus. CNTs impair neuronal exocytosis through specific proteolysis of essential proteins called SNAREs. SNARE assembly into a low-energy ternary complex is believed to catalyse membrane fusion, precipitating neurotransmitter release; this process is attenuated in response to SNARE proteolysis. Site-specific SNARE hydrolysis is catalysed by the CNT light chains, a unique group of zinc-dependent endopeptidases. The means by which a CNT properly identifies and cleaves its target SNARE has been a subject of much speculation; it is thought to use one or more regions of enzyme-substrate interaction remote from the active site (exosites). Here we report the first structure of a CNT endopeptidase in complex with its target SNARE at a resolution of 2.1 A: botulinum neurotoxin serotype A (BoNT/A) protease bound to human SNAP-25. The structure, together with enzyme kinetic data, reveals an array of exosites that determine substrate specificity. Substrate orientation is similar to that of the general zinc-dependent metalloprotease thermolysin. We observe significant structural changes near the toxin's catalytic pocket upon substrate binding, probably serving to render the protease competent for catalysis. The novel structures of the substrate-recognition exosites could be used for designing inhibitors specific to BoNT/A.


  • Organizational Affiliation

    Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NEUROTOXIN BONT/A424Clostridium botulinumMutation(s): 2 
UniProt
Find proteins for P0DPI1 (Clostridium botulinum (strain Hall / ATCC 3502 / NCTC 13319 / Type A))
Explore P0DPI1 
Go to UniProtKB:  P0DPI1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DPI1
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Synaptosomal-associated protein 2559Homo sapiensMutation(s): 0 
Gene Names: SNAP25SNAP
UniProt & NIH Common Fund Data Resources
Find proteins for P60880 (Homo sapiens)
Explore P60880 
Go to UniProtKB:  P60880
PHAROS:  P60880
GTEx:  ENSG00000132639 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP60880
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.218 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86α = 90
b = 86β = 90
c = 165.4γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
CNSrefinement
CCP4data scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-12-21
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-01-31
    Changes: Advisory, Experimental preparation
  • Version 1.4: 2021-10-20
    Changes: Advisory, Database references, Derived calculations
  • Version 1.5: 2024-02-14
    Changes: Data collection