› 5v8r

X-ray diffraction
1.9Å resolution

Small Molecule Inhibitor ABS-143 Bound to the Botulinum Neurotoxin Serotype A Light Chain

Released:
DOI: 10.2210/pdb5v8r/pdb
Model geometry
Fit model/data
PDB entry 5v8r coloured by chain, front view.
PDB entry 5v8r coloured by chain, side view.
PDB entry 5v8r coloured by chain, top view.
Source organism: Clostridium botulinum
Primary publication:
Small molecule metalloprotease inhibitor with in vitro, ex vivo and in vivo efficacy against botulinum neurotoxin serotype A.
Jacobson AR, Adler M, Silvaggi NR, Allen KN, Smith GM, Fredenburg RA, Stein RL, Park JB, Feng X, Shoemaker CB, Deshpande SS, Goodnough MC, Malizio CJ, Johnson EA, Pellett S, Tepp WH, Tzipori S
Toxicon 137 36-47 (2017)
PMID: 28698055

Function and Biology Details

Reaction catalysed: 
Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domain:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-144070 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Botulinum neurotoxin A light chain Chains: A, B
Molecule details ›
Chains: A, B
Length: 444 amino acids
Theoretical weight: 50.82 KDa
Source organism: Clostridium botulinum
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P0DPI1 (Residues: 1-424; Coverage: 33%)
Gene names: CBO0806, CLC_0862, bna, botA
Sequence domains: Clostridial neurotoxin zinc protease
Structure domains: Metalloproteases ("zincins"), catalytic domain like

Ligands and Environments

2 bound ligands:
Ligand ZN 2 x ZN
Ligand 90J 2 x 90J
No modified residues

Experiments and Validation Details

wwPDB Validation report is not available for this entry.
X-ray source: NSLS BEAMLINE X29A
Spacegroup: P21
Unit cell:
a: 73.534Å b: 67.635Å c: 98.112Å
α: 90° β: 104.91° γ: 90°
R-values:
R R work R free
0.177 0.175 0.222
Expression system: Escherichia coli BL21(DE3)

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Citations

3 review citations

Targeting Metalloenzymes for Therapeutic Intervention.
Chen et al. (2019)
2 more