› 5v8p

X-ray diffraction
2.5Å resolution

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

Released:
DOI: 10.2210/pdb5v8p/pdb
PDB entry 5v8p coloured by chain, front view.
PDB entry 5v8p coloured by chain, side view.
PDB entry 5v8p 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 90G 2 x 90G
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RUH2R
Spacegroup: P21
Unit cell:
a: 73.172Å b: 67.327Å c: 98.14Å
α: 90° β: 105.6° γ: 90°
R-values:
R R work R free
0.205 0.202 0.252
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

2 review citations

Insights into the Role of Tick Salivary Protease Inhibitors during Ectoparasite-Host Crosstalk.
Jmel et al. (2021)
1 more

1 mention without citation

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